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Archive for the ‘Longevity Genetics’ Category

Mutation explains why some men live to 100 – ISRAEL21c

Sunday, July 30th, 2017

Just as smaller animals of a given species generally live longer than their larger cousins, one might expect that taller humans are genetically programmed to sacrifice longevity for height.

But its not that simple.

A major multinational study of 841 men and women from across four populations found lower levels of insulin-like growth factor 1 (IGF-1) in men living to age 100 and yet most of them were taller than men in the younger control group.

The apparent explanation for this head-scratcher is that some long-lived men and only men have a genetic mutation that makes their growth hormone receptors more sensitive to the effects of the hormone. The cells absorb less growth hormone, yet protein expression is increased by several times.

This mutation seems to be responsible for their ability to live about 10 years longer than the control group of 70-year-old men without the mutation, even though they have a lower amount of growth hormone and are about 3 centimeters (1.18 inches) taller.

The lead author of the study is Prof. Gil Atzmon of Albert Einstein College of Medicine in New York and head of the Laboratory of Genetics and Epigenetics of Aging and Longevity at the University of Haifa. Since 2001, Atzmon has been studying the human genome and its impact on aging and longevity.

Longevity genes

The researchers working with Atzmon looked at four elderly populations: 567 Ashkenazi Jews in the Longevity Genes Project at Einstein, 152 from a study of Amish centenarians, and the rest from an American cardiovascular health study and a French longevity study.

In 2008, the Longevity Genes Project found a genetic mutation in the IGF-1 receptor of some women, though its not the same as the one affecting mens lifespan.

We knew in the past that genetic pathways associated with growth hormone were also associated with longevity and now we have found a specific mutation whose presence or absence is directly related to it, said Atzmon.

This study makes it an established fact that there is a relationship between the function of the growth hormone and longevity. Our current goal is to fully understand the mechanism of the mutation we found to express it, so that we can allow longevity while maintaining quality of life, he added.

The 16 researchers involved the study, published June 16 in Science Advances, are associated with institutions in Israel and France as well as the US states of New York, Maryland, California, Vermont, Massachusetts and Washington.

Clue to longer life

While more research is needed to understand why the receptor mutation affects longevity and why it happens only in men, the study suggests that making a slight change in this specific piece of DNA could possibly make people live longer.

Although the presence of the mutation almost certainly ensured longevity, Atzmon stressed that many other factors affect longevity and that many men without the mutation also live to 100 and older.

Atzmon is one of the principal researchers in the Longevity Genes Project at Einstein along with Israeli endocrinology specialist Dr. Nir Barzilai.

Their groundbreaking 10-year study of healthy Ashkenazi Jews between the ages of 95 and 112 and their children attempted to understand why humans dont all age at the same rate, and why only one in 10,000 individuals lives to 100.

The centenarians were found to have genetic protective factors (longevity genes) that overcame factors such as diet and lifestyle.

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How to live old – The Sherbrooke Times

Sunday, July 30th, 2017

Jacques Laplante andDavid Riendeau

Sunday, 30 July, 2017 08:00

UPDATESunday, 30 July, 2017 08:00

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The secret of the longevity of centenarians? A combination of genetics, healthy living and unshakable confidence in itself, said Dr. Judes Poirier, to whom we owe the book Young and centenary.

The book of popular science explains the mechanisms of human ageing through the phenomenon of centenarians, always more numerous in our society.

For 15 years, a colleague has sought to know the secret of longevity of several century-old French. The answers were very varied. One swore by a glass of red daily, while for the other, it was his spoonful of honey, says Judes Poirier, director of research at the Institute of mental health Douglas.

Archival Photo Chantal Poirier

Dr. Judes Poirier has explored the factors that contribute to the longevity of centenarians

However, all claimed to have worked for all their lives and get a great pride.

The same exercise has been done, this time with their children and grandchildren.

They held that the centenarians were people decidedly positive, determined and confident in their abilities. They lived fully in the moment, and remain constantly active.

The same explanations of regularity, temperance, and work come back in most of the major studies on centenarians conducted in various countries, notes Dr. Poirier.

A complex issue

The causes responsible for the aging are multiple and it is possible to age beautifully, emphasizes the scientist, citing by example the benefits of physical activity.

The exercise by itself does not prolong the life of the human. However, it improves the quality of life of the past few years. The goal is to mitigate the risk of emerging chronic diseases such as obesity and diabetes.

Young hundred-year-old also addressed the issue of blue zones, these areas of the world where the life expectancy of their inhabitants is superior to the rest of the world.

If they have the same genes, their mode of life is different, observes Judes Poirier, who has compiled some general trends in their habits, such as having life goals clear and to live a long time with their family.

Six tips for aging well

Number of centenary over time

In 2061, it is estimated that there will be nearly 34 000 centenarians in Quebec.

Source : Institut de la statistique du Qubec

Irene Richard, 106 years

Photo Pierre-Paul Poulin

The life of Irene, Richard, 106 years, can be summed up in two words : hard work. Click here to read more

Geraldine Crevier, 100 years

Photo Chantal Poirier

When asked, Geraldine Crevier, 100 years old, replied that there was no secret to his longevity, especially as she smoked until the age of 50 years. Curious by nature, this is perhaps not his thirst for learning that keeps it alive, but it is certainly making his old days as interesting. Click here to read more

Winnifred Rees, 100 years

Photo Marc QMI Agency, Desrosiers

My secret is prayer and the Bible. I believe in the power of God, says Winnifred Rees, who will soon be 101 years old. Click here to read more

Joacquina Lalande, 106 years

Photo Chantal Poirier

From the top of its 106 years, Joacquina Lalande refuses to impose. The only daughter of a family of seven children, she has always been a go-getter who wasnt afraid of hard work. Click here to read more

Sarah Patenaude, 110 years

Photo Agence QMI, Marc Desrosiers

According to Sarah Patenaude, to live well, it takes work, but do not lay claim to. It is necessary to take a vacation, eat fruit and meat and well practice his or her religion, whatever it may be. Anyway, there is some good in all religions, she said. Click here to read more

Gisele Bright, 101 years

Photo Ben Pelosse

If several of the centenarians attribute their longevity to a trick or a secret of any kind, such as a healthy life, away from tobacco and alcohol, this is not the case of Gisle Brilliant, which celebrated its 101 years in may. Click here to read more

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The 16 genetic markers that can cut a life story short – Medical Xpress – Medical Xpress

Sunday, July 30th, 2017

Credit: CC0 Public Domain

The answer to how long each of us will live is partly encoded in our genome. Researchers have identified 16 genetic markers associated with a decreased lifespan, including 14 new to science. This is the largest set of markers of lifespan uncovered to date. About 10 percent of the population carries some configurations of these markers that shorten their life by over a year compared with the population average. Spearheaded by scientists from the SIB Swiss Institute of Bioinformatics, the Lausanne University Hospital (CHUV), the University of Lausanne and the EPFL, the study provides a powerful computational framework to uncover the genetics of our time of death, and ultimately of any disease. The study is published today in Nature Communications.

Why do some of us live longer than others? While the environment in which we live including our socio-economic status or the food we eat plays the biggest part, about 20 to 30 percent of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity.

"Until now, the most comprehensive studies had found only two hits in the genome," points out Prof. Zoltn Kutalik, Group Leader at SIB and assistant professor at the Institute of Social and Preventive Medicine (CHUV).

In a new study, a team of scientists, led by Kutalik, has used an innovative computational approach to analyse a dataset of 116,279 individuals and probe 2.3 million human SNPs.

An unparalleled number of SNPs associated with lifespan (16) were uncovered, including 14 new to science. "In our approach, we prioritized changes in the DNA known to be linked to age-related diseases in order to scan the genome more efficiently," says Kutalik. "This is the largest set of lifespan-associated genetic markers ever uncovered."

About 1 in 10 people carry some configurations of these markers that shorten their life by over a year compared with the population average. In addition, a person inheriting a lifespan-shortening version of one of these SNPs may die up to seven months earlier.

The approach also enabled the researchers to explore how the DNA changes affected lifespan in a holistic way. They found that most SNPs had an effect on lifespan by impacting more than a single disease or risk factor, for example through being more addicted to smoking as well as through being predisposed to schizophrenia.

The discovered SNPs, combined with gene expression data, allowed the researchers to identify that lower brain expression of three genes neighbouring the SNPs (RBM6, SULT1A1 and CHRNA5, involved in nicotine dependence) was causally linked to increased lifespan.

These three genes could therefore act as biomarkers of longevity, i.e. survival beyond 85-100 years. "To support this hypothesis, we have shown that mice with a lower brain expression level of RBM6 lived substantially longer," comments Prof. Johan Auwerx, professor at the EPFL.

"Interestingly, the gene expression impact of some of these SNPs in humans is analogous to the consequence of a low-calorie diet in mice, which is known to have positive effects on lifespan," adds Prof. Marc Robinson-Rechavi, SIB Group Leader and professor at the University of Lausanne.

"Our findings reveal shared molecular mechanisms between human and model organisms, which will be explored in more depth in the future," concludes Prof. Bart Deplancke, SIB Group Leader and professor at the EPFL.

This study, which is a part of the AgingX Project supported by SystemsX.ch (the Swiss Initiative in Systems Biology), therefore brings us a step closer to grasping the mechanisms of human aging and longevity. It also proposes an innovative computational framework to improve the power of genomewide investigations of diseases more generally. As such, the framework could have promising applications in the field of personalized medicine.

Explore further: Study shows smoking doesn't always mean a shortened life span or cancer

More information: Aaron F. McDaid et al. Bayesian association scan reveals loci associated with human lifespan and linked biomarkers, Nature Communications (2017). DOI: 10.1038/NCOMMS15842

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Health Shorts: Stem cell ‘cures,’ Sugar spike, Longevity – Sarasota Herald-Tribune

Sunday, July 30th, 2017

Sketchy stem cell "cures" infiltrate trial database

Stem cell clinics offering unapproved treatments for ailments from hip pains to erectile dysfunction increasingly use a federal clinical-trials database as a marketing tool a strategy that confuses patients and exposes them to "unjustifiable" safety risks and costs, according to a new study.

At least 18 purported clinical trials all of which involve unregulated therapies and require patients to pay to enroll are listed on ClinicalTrials.gov, the comprehensive registry for public and private clinical trials that is run by the National Institutes of Health, according to the journal Regenerative Medicine.

Leigh Turner, who authored the study and is an associate professor at the University of Minnesota's Center for Bioethics and School of Public Health, said NIH should use much tougher screening tools to exclude from its database unapproved treatments.

"Do we really want ClinicalTrials.gov to be 'caveat emptor,' where no one is paying attention to the substance of studies being listed?" said Turner. "A lot of these studies are just marketing pitches designed to appeal to people with COPD, multiple sclerosis and Parkinson's disease."

Most legitimate trials do not charge patients, though they might face incidental costs such as travel.

Laurie Mcginley, The Washington Post

Canadian study find a sugar spike after NAFTA

The North American Free Trade Agreement may have dramatically changed the Canadian diet by boosting consumption of high-fructose corn syrup, a new study suggests.

That boost arrested a years-long decline in total sugar consumption. And it shifted Canadians away from liquid sweeteners such as maltose and molasses toward high-fructose corn syrup, a sweetener that has been linked to the obesity epidemic.

The peer-reviewed study, published in the Canadian Medical Association Journal, found that as tariffs on high-fructose corn syrup dropped over a four-year period, consumption grew: from 21.2 calories of corn syrup per day in 1994, to 62.9 calories per day by 1998.

NAFTA may thus have contributed to growing obesity and diabetes rates over that time, its authors say.

"There are free-trade deals being negotiated all over the world, and NAFTA has been used as a blueprint for many of them," said Pepita Barlow, a doctoral student at Oxford University and the lead researcher on the paper. "In some ways, this is an opportunity to think about who benefits from these deals, and who loses and how we can craft them to better promote health and wellness."

Caitlin Dewey, The Washington Post

The smarter the kid, the longer the life?

Intelligent children tend to live longer than their less gifted peers, a new study suggests.

Scottish researchers began their study with 75,252 men and women born in 1936 94 percent of the Scottish population born that year who had taken standardized intelligence tests in 1947. By 2015, they were able to confirm a cause of death for 25,979 of them; 30,464 were still living in Britain.

After controlling for many health, socioeconomic and behavioral characteristics, they found that lower scores on the childhood intelligence test were associated with death from heart disease, stroke, respiratory disease, lung cancer and stomach cancer. All of these diseases are highly associated with smoking, and smoking did partially explain the association with mortality. But even after controlling for smoking, the link to lower scores on the intelligence test did not disappear.

The study, in BMJ, found no association of lower intelligence with cancers not related to smoking or with suicide, but there was a strong association with death by accidental injury.

The reasons for the link are far from clear. We dont know yet why intelligence from childhood and longevity are related, and we are keeping an open mind, said the senior author, Ian J. Deary, a professor of differential psychology at the University of Edinburgh. Lifestyles, education, deprivation and genetics may all play a part.

Nicholas Bakalar, The New York Times

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Swiss-led research team identifies new life-expectancy markers – The Hans India

Sunday, July 30th, 2017

Geneva : A Swiss-led team conducting research on life expectancy said on Thursday it had identified the largest-ever number of genetic markers that are almost entirely new to science.

The answer to how long each person will live is partly encoded in their genomes or their genetic material, Xinhua quoted the researchers as saying, who published the findings in journal Nature Communication.

The study was led by scientists from the Swiss Institute of Bioinformatics (SIB), Lausanne University Hospital (CHUV), the University of Lausanne and the Swiss Federal Institute of Technology in Lausanne (EPFL). The study used advanced computer capabilities to uncover the genetics of our time of death and ultimately of any disease.

During the research, the scientists identified 16 genetic markers associated with a decreased lifespan, including 14 that are new to science.

"This is the largest set of markers of lifespan uncovered to date," said the SIB in the statement.While the environment in which we live, including our socio-economic status or the food we eat, plays the biggest part in explaining longevity, about 20 to 30 per cent of the variation in human lifespan comes down to genomes.

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Study probes Greenland sharks’ secret to long life – NATIONAL – The … – The Hindu

Sunday, July 9th, 2017

The Hindu
Study probes Greenland sharks' secret to long life - NATIONAL - The ...
The Hindu
Greenland sharks, the longest living vertebrates on Earth, which live for up to 400 years, could hold the secret to long life, geneticists mapping their DNA say.

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Longevity Genes Predict Whether You’ll Live Past 100

Saturday, July 8th, 2017

Reaching immortality is still in the realm of science fiction. But using clues from our genes, scientists are one step closer to understanding why some of us live to be centenarians while others don't.

Using a specific set of genetic markers, scientists predicted with 77-percent accuracy whether someone would live to a very old age.

The findings do not mean that lifestyle factors, such as healthy diet and exercise, are not important for long life. Indeed, 23 percent of the time the genetic markers didn't predict longevity. So those long-lifers without the centenarian genes might have practiced healthy habits that allowed them to lead a longer life. [Learn more facts about centenarians]

But they do suggest our genes play an important role when it comes to living well past the average lifespan. With more research, one day people might be able to determine whether they have the genetic potential to become a centenarian.

Additionally, learning more about how centenarians ward off diseases, including dementia, heart disease and cancer, well into their elder years, might help the rest of us delay disease.

"I'm very hopeful that understanding how and why centenarians are able to do that will lead to strategies and therapies, including screening and figuring out who could be helped by whatever therapies [there] are down the road," study researcher Tom Perls, of Boston University School of Medicine, said in a press briefing Wednesday about the study.

The results will be published this week in an early online edition of the journal Science.

Longevity genetics

The researchers compared the genomes of 1,055 centenarians (average age of 103) with those of non-centenarian controls.

They identified differences in the genetic code, known as genetic variants or markers, that were common in centenarians but not in the average population.

Using a computer model, they found 150 of these markers could predict 77 percent of the time whether a person lived into their late 90s and beyond.

Additionally, they saw 90 percent of the centenarians could be categorized into one of 19 groups based on which genetic variants they had. In other words, each group had a distinguishing "genetic signature" made up of certain genetic markers.

Differences in these genetic signatures may relate to differences in the way extreme longevity manifests itself. For instance, some genetic signatures were associated with extremely old age (living 110 years or more), while others were associated with a late onset of diseases such as dementia.

So can someone live to old age without these markers? Perhaps. About 30 of the centenarians had almost none of the longevity associated markers. In these cases, extreme old age might be influenced by other markers that have yet to be identified, or by the subject's lifestyle.

The researchers were also curious if centenarians had fewer markers that are known to be linked with diseases. However, in this respect, they found little difference between the centenarians and the control group.

This might mean that centenarians owe their exceptional lifespan not to less "bad genes," but to the presence of "good genes" that override the harmful ones.

This results suggests "that what makes people live very long lives is not a lack of genetic predisposition to diseases, but rather an arrangement of longevity associated variants that may be protective, it may even cancel the negative effect of disease-associated variants," said study researcher Paola Sebastiani, of Boston University School of Public Health, who also spoke at the briefing.

Future outlook

The researchers caution that before a genetic test for longevity is developed, scientists need to have a better understanding of what kind of effect the information could have on society, such as in the context of health care.

They hope the study spurs additional research into these genetic markers and how they might biologically contribute to longevity.

"I think that we're quite a ways away still in understanding what pathways governed by these genes are involved, and how the interaction of these genes, not just with themselves, but with environmental factors, are all playing a role in this longevity puzzle," Perls said.

The study was funded by grants from the National Institute of Aging (NIA) and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

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This Study Could Help Extend the Human Lifespan – Futurism

Saturday, July 8th, 2017

In BriefResearchers have identified a single gene deletion in E. colibacteria that influence longevity in C. elegans worms. This pointsto the role of gut bacteria in life extension and points to thepossibility of a life-extending probiotic in the future.

Researchers at the Baylor College of Medicine have found the key to longevity in Caenorhabditis elegans (C. elegans) worms and maybe, someday, humans. The team noticed that genetically identical worms would occasionally live for much longer, and looked to their gut bacteria to find the answer. They discovered that a strain of E. coli with a single gene deletion might be the reason that its hosts lives were being significantly extended.

This study is one among a number of projects that focus on the influence of the microbiome the community of microbes which share the body of the host organism on longevity. Ultimately, the goal of this kind of research is to develop probiotics that could extend human life. Ive always studied the molecular genetics of aging, Meng Wang, one of the researchers who conducted the study, told The Atlantic. But before, we always looked at the host. This is my first attempt to understand the bacterias side.

Even in cases like this, where it seems fairly obvious that the microbiome is influencing longevity, parsing out the details of how and why this happens among a tremendous variety of chemicals and microbe species is extremely complex. The team, in this case, was successful because they simplified the question and focused on a single relationship.

Genetically engineering bacteria to support and improve human health and even to slow aging and turning it into a usable, life-extending probiotic wont be easy. It is extremely difficult to make bacteria colonize the gut in a stable manner, which is a primary challenge in this field. The team, in this case, is looking to the microbiome, because the organisms used would be relatively safe to use because they would originate in the gut.

Clearly, researchers dont know yet whether these discoveries will be able to be applied to people, though it seems promising. Despite the obvious differences between the tiny C. elegans worm and us, its biology is surprisingly similar; many treatments that work well in mice and primates also work in the worm. The team will begin experiments along these same lines with mice soon.

Other interesting and recent research hoping to stop or slow the march of time includes work with induced pluripotent stem (iPS) cells, antioxidants that target the mitochondria, and even somewhat strangework with cord blood. It seems very likely that we wont have a single solution offering immortality anytime soon, but instead a range of treatment options that help to incrementally hold back time. And, with an improving quality of life, this kind of life extension sounds promising.

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Sharks could hold genetic secret to long life: Study – The Hindu

Saturday, July 8th, 2017

The Hindu
Sharks could hold genetic secret to long life: Study
The Hindu
The genetic sequences helped the researchers understand whether the Greenland shark has evolved specific metabolic adaptations towards extreme longevity. They are now attempting to find the genes that hold the secret to why the sharks live so long.

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11 Basic Guidelines for General Health and Longevity …

Sunday, July 2nd, 2017

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A healthy lifestyle is essential to achieving optimal wellbeing and longevity. This infographic, "11 Basic Guidelines for General Health and Longevity," gives you useful tips to help you live a long and healthy life. Use the embed code to share it on your website or visit our infographic page for the high-res version.

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When it comes to health and longevity, there is no quick fix and no fountain of youth that will help you become healthy overnight. Being fit and healthy in order to reach a ripe old age takes effort and attention this is something that I repeatedly tell my readers.

But here's the good news: there are a few simple lifestyle changes you can make to improve not only the quantity, but also the quality of your years. These changes are pretty basic, but can have a profound effect on your overall health once implemented.

One of the most basic health principles (and, sadly, the one people most often ignore) is eating a diet of whole, nutritious foods rather than unhealthy processed foods. Keep in mind that processed and junk foods are loaded with grains, sugar, and unhealthy calories that increase your insulin levels, which not only accelerates the aging process but also increases your risk of obesity and chronic disease.

I also highly advise against consuming genetically engineered (GE) foods. Not only are GE foods less nutritious than organically-grown foods, but they also pose many health risks. In fact, most processed foods today contain GE ingredients regardless of the fact that these GE components have not undergone long-term safety studies.

The best diet I would recommend for optimal health and longevity is one that's focused on whole, unprocessed foods preferably organic vegetables, grass-fed meats, raw dairy, and nuts acquired from healthy, sustainable, local sources. I also recommend consuming a good portion of your food raw, as well as adding naturally fermented foods to meals.

By implementing these basic diet changes, you can make a big leap toward longevity and optimal health.

For more useful tips in healthy eating, I advise you to follow the Mercola Nutrition Plan, which will guide you in choosing the right foods that will suit your unique biological makeup. The Mercola Nutrition Plan addresses your unique biochemical needs based on your specific genetics, allowing you to cure your health problems at the foundational level and giving you a more permanent solution for regaining your health.

Equally important to consuming a healthy diet is being physically active. According to studies, people who are sedentary are found to have a shorter lifespan. In fact, one study shows that reducing the average time you spend sitting down to less than three hours a day may increase your life expectancy by two years, and reducing the time you spend watching TV to less than two hours a day could increase it by 1.4 years.

I understand how difficult it is to avoid sitting down for prolonged periods, as computer work is very predominant today. Even I am guilty of spending a significant portion of my day sitting down. But to make up for it, I make sure that I get enough exercise daily. I also take frequent breaks every hour to stand up at my desk. I highly recommend Foundation Exercises, developed by chiropractor Dr. Eric Goodman, as well as short-burst high-intensity exercises, like Peak Fitness. You can read more about these techniques by subscribing to the Mercola daily newsletter.

Exercise also has some anti-aging effects, as proven by many studies. One study published in the American Journal of Physiology says that exercise triggers mitochondrial biogenesis, a decline of which is common in aging. This means that exercise can reverse significant age-associated declines in mitochondrial mass and, in effect, stop aging in its tracks.

Keep in mind that modifying your diet and exercising are not the only important factors of health and longevity. There are many other things that you need to implement to ensure that you will be optimally healthy.

I have created this infographic, 11 Basic Guidelines for General Health and Longevity, to summarize all the components that need to be addressed if you want to live a long and healthy life. Here, you will learn:

These guidelines form the basic tenets of optimal health. They are tried-and-tested foundational strategies that will not change, no matter what improvements modern science comes up with.

I urge you to follow these tips to significantly decrease your likelihood of disease and premature aging. Use these as the foundation of your overall wellness plan, and you will surely succeed in improving your health.

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There’s No Known Limit To How Long Humans Can Live | Time.com – TIME

Sunday, July 2nd, 2017

Karen Kaspar / EyeEmGetty Images/EyeEm

Last October, scientists made a splash when they determined that on average, people can only live for about 115 years . That was the magic age at which the human body and brain just petered out; it wasnt designed to chug along much longer than that, they said.

That conclusion, published in the journal Nature , sparked hot debate among longevity researchers. Some felt the results vindicated what they felt to be the case, while others took issue with pinpointing a limitand such a specific one, at that.

Now, in the new issue of Nature , the editors invited scientists who criticized the original authors methods to lay out their arguments for why there isn't necessarily a limit to human aging. In the five resulting critiques, researchers tease apart the original authors methods, noting that they made assumptions that weren't warranted and overreached in their conclusions. (The researchers who concluded that human lifespan maxes out at 115 years stand by their findings, and they responded to each of the current authors criticisms.)

The new papers dont argue that human lifespan is limitless. But they note that its premature to accept that a maximum lifespan for humans exists. Its equally possible, they say, that humans will continue to live longer, and therefore might survive beyond 115 years. It was reasonable that when everybody lived to 50 that the very long lived, for whatever reasongenetics or luckwould make it to 80," says Siegfried Hekimi, professor of genetics at McGill University in Canada and one of the authors of a criticism. "If people live on average to 80 or 90, like they do now, then the very long lived make it to 110 or 120. So if the average lifespan keeps expanding, that would mean the long-lived would live even longer, beyond 115 years."

Overall, trends in longevity have been going up, and average lifespan has inched upward since even the 1990s. Back then, life expectancy in the U.S. was just around 50 years, while babies born today live to about 79 years on average. In any given year, however, if you look at the longest-lived, or the age at which the oldest person died, there may be considerable variation. There may be several years in which the maximum lifespan drops a bit, and other years in which it jumps.

MORE: How Silicon Valley Is Trying to Hack Its Way Into a Longer Life

The maximum lifespan in a population varies so much year to year that if you take the wrong snapshot of dataas Hekimi contends the original authors didit may look like there is a flattening of the age at which the longest lived die. If you throw a die several times every year that represents maximum lifespan, by chance alone you will see a lot of spread," he says. "Sometimes it will be low, sometimes it will be high.

For example, in coming up with the maximum lifespan of 115 years, the original papers researchers divided their population data into two groups: from 1968 to 1994 and 1995 to 2006. They determined that maximum lifespan peaked in the first era and started to plateau in the next. However, that coincides with the years in which Jeanne Calment, the oldest-lived human, was alive. She passed away in 1997 at age 122, so the plateau in maximum lifespan that the original researchers saw could be wholly attributed to her, Hekimi says. He and the other authors argue that the conclusion that human lifespan stops at 115 years was based on misinterpreting the data by seeing a plateau at 115 years where there was none.

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Could a High IQ Mean a Longer Life? – Sioux City Journal

Sunday, July 2nd, 2017

THURSDAY, June 29, 2017 (HealthDay News) -- A high IQ might do more than help you garner good grades: New research suggests it might also lengthen your life.

Scottish researchers analyzed data on nearly 66,000 people who were born in that country in 1936, took an IQ test at age 11, and were followed up to age 79 or death. The investigators discovered that children with high IQs were more likely to live longer than their less intelligent peers.

Specifically, a higher IQ test score in childhood was associated with a 28 percent reduced risk of death from respiratory disease, a 25 percent lower risk of death from heart disease and a 24 percent reduced risk of death from stroke.

But the study didn't prove that high IQ caused this reduced risk, just that an association existed.

A higher IQ in childhood was also significantly associated with a lower risk of death from injury, smoking-related cancers (particularly lung and stomach), digestive disease and dementia. There was no evidence of a link between childhood intelligence and death from cancers not related to smoking.

The findings suggest that lifestyle -- especially smoking -- plays a major role in how intelligence affects the risk of death, according to the University of Edinburgh team. It was led by Ian Deary, a professor of differential psychology.

The findings were published June 28 in the journal BMJ.

In an editorial accompanying the study, Swedish researchers wrote that "childhood IQ is strongly associated with causes of death that are, to a great extent, dependent on already known risk factors."

But according to Daniel Falkstedt, an assistant professor, and Anton Lager, head of the department of public health sciences at Karolinska Institute in Stockholm, "It remains to be seen if this is the full story or if IQ signals something deeper, and possibly genetic, in its relation to longevity."

Senior study author Deary agreed, telling The New York Times, "We don't know yet why intelligence from childhood and longevity are related, and we are keeping an open mind. Lifestyles, education, deprivation and genetics may all play a part."

The U.S. National Institute on Aging has more about longevity.

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Could a High IQ Mean a Longer Life? - Sioux City Journal

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Researchers Find Genetic Mutation That Encourages Longevity In Men – Yeshiva World News

Sunday, July 2nd, 2017

Researchers have found a mutation in the gene for the growth hormone receptor that promotes longevity, increasing mens lifespan by an average of 10 years.

This finding emerged from a new study led by Prof. Gil Atzmon of the University of Haifa. We were aware before that variants involved with genetic paths related to the growth hormone are also associated with longevity. Now we have found a specific variant whose presence or absence is directly connected to it, Prof. Atzmon explains.

Prof. Atzmon, head of the Laboratory of Genetics and Epigenetics of Aging and Longevity at the University of Haifa, and other colleagues at Albert Einstein College of Medicine have already found that dysfunction in the biological paths associated with the growth hormone and with insulin-like growth factor-1 (IGF-1) contribute to longevity. Until now, however, these paths were tested in the laboratory, and few mechanism responsible for this process had been identified in the human body.

In the present study, published in the journal Science Advances from the Science group, the researchers identified for the first time a genetic variation that modify the growth hormone function and encourages longevity in men. The initial research population (established by Professor Nir Barzilai at Einstein) comprised 102 American male Jews at the age of 100. The results were then compared with three additional populations of people at the age of 100 from around the world.

In all the groups, the deletion of exon 3 from the growth hormone receptor gene was found to be significantly more common among men (and not women) at the age of 100, compared to the control group of 70-year-olds. On average, people born with this variation lived ten years longer than those without it. According to Prof. Atzmon, this variation is certainly not the only reason for longevity, and many of the participants in the study survived beyond the age of 100 without this variation. However, the presence of the variant ensured longevity with virtual certainty.

The examination of the action of the variation showed that it has an unusual impact. In nature, lower strains of the same species usually live longer. For example, ponies live longer than horses, smaller breeds of dogs live longer than larger ones, and the same phenomenon is found among various rodents and insects. In this case, the variation in the receptor allowed the cells to absorb less growth hormone, however, when the hormone absorbed the protein expression was several times higher. The result: people born with the mutation who lived for around ten years more than others were also approximately 3 cm taller than those born without the receptor.

This study nicely wraps up the connection between growth hormone function and longevity. Our goal now is really to understand the mechanism of the variation we found, so that we can implement it and enable longevity while maintaining quality of life, Prof. Atzmon concluded.

(YWN Israel Desk, Jerusalem)

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Researchers Find Genetic Mutation That Encourages Longevity In Men - Yeshiva World News

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Haifa U Researchers Find Genetic Mutation that Encourages Longevity in Men – The Jewish Press – JewishPress.com

Sunday, July 2nd, 2017

Photo Credit: Free image from Pixaboy

Researchers have found a mutation in the gene for the growth hormone receptor that promotes longevity, increasing mens lifespan by an average of 10 years. This finding emerged from a new study led by Prof. Gil Atzmon of the University of Haifa. We were aware before that variants involved with genetic paths related to the growth hormone are also associated with longevity. Now we have found a specific variant whose presence or absence is directly connected to it, Prof. Atzmon explains.

Prof. Atzmon, head of the Laboratory of Genetics and Epigenetics of Aging and Longevity at the University of Haifa, and other colleagues at Albert Einstein College of Medicine have already found that dysfunction in the biological paths associated with the growth hormone and with insulin-like growth factor-1 (IGF-1) contribute to longevity. Until now, however, these paths were tested in the laboratory, and few mechanism responsible for this process had been identified in the human body.

In the present study, published in the journal Science Advances from the Science group, the researchers identified for the first time a genetic variation that modify the growth hormone function and encourages longevity in men. The initial research population (established by Professor Nir Barzilai at Einstein) comprised 102 American male Jews at the age of 100. The results were then compared with three additional populations of people at the age of 100 from around the world.

In all the groups, the deletion of exon 3 from the growth hormone receptor gene was found to be significantly more common among men (and not women) at the age of 100, compared to the control group of 70-year-olds. On average, people born with this variation lived ten years longer than those without it. According to Prof. Atzmon, this variation is certainly not the only reason for longevity, and many of the participants in the study survived beyond the age of 100 without this variation. However, the presence of the variant ensured longevity with virtual certainty.

The examination of the action of the variation showed that it has an unusual impact. In nature, lower strains of the same species usually live longer. For example, ponies live longer than horses, smaller breeds of dogs live longer than larger ones, and the same phenomenon is found among various rodents and insects. In this case, the variation in the receptor allowed the cells to absorb less growth hormone, however, when the hormone absorbed the protein expression was several times higher. The result: people born with the mutation who lived for around ten years more than others were also approximately 3 cm taller than those born without the receptor.

This study nicely wraps up the connection between growth hormone function and longevity. Our goal now is really to understand the mechanism of the variation we found, so that we can implement it and enable longevity while maintaining quality of life, Prof. Atzmon concluded.

Read the original here:
Haifa U Researchers Find Genetic Mutation that Encourages Longevity in Men - The Jewish Press - JewishPress.com

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68-Year Study: Childhood Intelligence and Longevity Related – Newsmax

Sunday, July 2nd, 2017

Smart children tend to live longer than their less intelligent peers, a new study suggests.

The analysis by Scottish researchers, published by medical journal BMJ, tracked 75,252 men and women born in 1936 who had taken standardized intelligence tests in 1947.

By 2015, researchers confirmed a cause of death for 25,979 of them; 30,464 were still living in Britain.

"In a whole national population year of birth cohort followed over the life course from age 11 to age 79, higher scores on a well validated childhood intelligence test were associated with lower risk of mortality ascribed to coronary heart disease and stroke, cancers related to smoking (particularly lung and stomach), respiratory diseases, digestive diseases, injury, and dementia," the researchers wrote.

According to The New York Times, even after controlling for smoking, the link to lower scores on the intelligence testsdidn't disappear. The study found no association of lower intelligence with cancers unrelated to smoking or with suicide, but there was a strong association with death by accidental injury.

"We dont know yet why intelligence from childhood and longevity are related, and we are keeping an open mind," senior author, Ian Deary of the University of Edinburgh told the Times.

"Lifestyles, education, deprivation and genetics may all play a part."

2017 Newsmax. All rights reserved.

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Lamarckism – Wikipedia

Thursday, January 5th, 2017

Lamarckism (or Lamarckian inheritance) is the idea that an organism can pass on characteristics that it has acquired during its lifetime to its offspring (also known as heritability of acquired characteristics or soft inheritance). It is named after the French biologist Jean-Baptiste Lamarck (17441829), who incorporated the action of soft inheritance into his evolutionary theories as a supplement to his concept of an inherent progressive tendency driving organisms continuously towards greater complexity, in parallel but separate lineages with no extinction. Lamarck did not originate the idea of soft inheritance, which proposes that individual efforts during the lifetime of the organisms were the main mechanism driving species to adaptation, as they supposedly would acquire adaptive changes and pass them on to offspring.

When Charles Darwin published his theory of evolution by natural selection in On the Origin of Species (1859), he continued to give credence to what he called "use and disuse inheritance," but rejected other aspects of Lamarck's theories. Later, Mendelian genetics supplanted the notion of inheritance of acquired traits, eventually leading to the development of the modern evolutionary synthesis, and the general abandonment of the Lamarckian theory of evolution in biology. Despite this abandonment, interest in Lamarckism has continued as studies in the field of epigenetics have highlighted the possible inheritance of behavioral traits acquired by the previous generation.[1][2][3][4][5] However, this remains controversial as science historians have asserted that it is inaccurate to describe transgenerational epigenetic inheritance as a form of Lamarckism.[6][7][8][9]

Between 1794 and 1796 Erasmus Darwin wrote Zoonomia suggesting "that all warm-blooded animals have arisen from one living filament... with the power of acquiring new parts" in response to stimuli, with each round of "improvements" being inherited by successive generations.[10] Subsequently, Jean-Baptiste Lamarck repeated in his Philosophie Zoologique of 1809 the folk wisdom that characteristics which were "needed" were acquired (or diminished) during the lifetime of an organism then passed on to the offspring. He incorporated this mechanism into his thoughts on evolution, seeing it as resulting in the adaptation of life to local environments.

Lamarck founded a school of French Transformationism which included tienne Geoffroy Saint-Hilaire, and which corresponded with a radical British school of anatomy based in the extramural anatomy schools in Edinburgh, Scotland, which included the surgeon Robert Knox and the comparative anatomist Robert Edmond Grant. In addition, the Regius Professor of Natural History at the University of Edinburgh, Robert Jameson, was the probable author of an anonymous paper in 1826 praising "Mr. Lamarck" for explaining how the higher animals had "evolved" from the "simplest worms"this was the first use of the word "evolved" in a modern sense. As a young student, Charles Darwin was tutored by Grant, and worked with him on marine creatures.

The Vestiges of the Natural History of Creation, authored by Robert Chambers in St Andrews, Scotland, and published anonymously in England in 1844, proposed a theory which combined radical phrenology with Lamarckism, causing political controversy for its radicalism and unorthodoxy, but exciting popular interest and preparing a huge and prosperous audience for Darwin.

Darwin's On the Origin of Species proposed natural selection as the main mechanism for development of species, but did not rule out a variant of Lamarckism as a supplementary mechanism.[11] Darwin called his Lamarckian hypothesis pangenesis, and explained it in the final chapter of his book The Variation of Animals and Plants under Domestication (1868), after describing numerous examples to demonstrate what he considered to be the inheritance of acquired characteristics. Pangenesis, which he emphasised was a hypothesis, was based on the idea that somatic cells would, in response to environmental stimulation (use and disuse), throw off 'gemmules' or 'pangenes' which travelled around the body (though not necessarily in the bloodstream). These pangenes were microscopic particles that supposedly contained information about the characteristics of their parent cell, and Darwin believed that they eventually accumulated in the germ cells where they could pass on to the next generation the newly acquired characteristics of the parents. Darwin's half-cousin, Francis Galton, carried out experiments on rabbits, with Darwin's cooperation, in which he transfused the blood of one variety of rabbit into another variety in the expectation that its offspring would show some characteristics of the first. They did not, and Galton declared that he had disproved Darwin's hypothesis of pangenesis, but Darwin objected, in a letter to the scientific journal Nature, that he had done nothing of the sort, since he had never mentioned blood in his writings. He pointed out that he regarded pangenesis as occurring in Protozoa and plants, which have no blood.[12]

The identification of Lamarckism with the inheritance of acquired characteristics is regarded by some as an artifact of the subsequent history of evolutionary thought, repeated in textbooks without analysis. American paleontologist and historian of science Stephen Jay Gould wrote that in the late 19th century, evolutionists "re-read Lamarck, cast aside the guts of it ... and elevated one aspect of the mechanicsinheritance of acquired charactersto a central focus it never had for Lamarck himself."[13] He argued that "the restriction of 'Lamarckism' to this relatively small and non-distinctive corner of Lamarck's thought must be labelled as more than a misnomer, and truly a discredit to the memory of a man and his much more comprehensive system."[14] Gould advocated defining "Lamarckism" more broadly, in line with Lamarck's overall evolutionary theory.

Lamarck incorporated two ideas into his theory of evolution, in his day considered to be generally true. The first was the idea of use versus disuse; he theorized that individuals lose characteristics they do not require, or use, and develop characteristics that are useful. His second point was to argue that the acquired traits were heritable. Examples of what is traditionally called "Lamarckism" would include the idea that when giraffes stretch their necks to reach leaves high in trees (especially Acacias), they strengthen and gradually lengthen their necks. These giraffes have offspring with slightly longer necks (also known as "soft inheritance"). Similarly, a blacksmith, through his work, strengthens the muscles in his arms, and thus his sons will have similar muscular development when they mature.

Lamarck stated the following two laws:

English translation:

In essence, a change in the environment brings about change in "needs" (besoins), resulting in change in behavior, bringing change in organ usage and development, bringing change in form over timeand thus the gradual transmutation of the species.

However, as historians of science such as Michael Ghiselin and Stephen Jay Gould have pointed out, none of these views were original to Lamarck.[17][18] On the contrary, Lamarck's contribution was a systematic theoretical framework for understanding evolution. He saw evolution as comprising two processes;

The idea that germline cells contain information that passes to each generation unaffected by experience and independent of the somatic (body) cells, came to be referred to as the Weismann barrier, and is frequently quoted as putting a final end to Lamarckism and theory of inheritance of acquired characteristics.

August Weismann conducted the experiment of removing the tails of 68 white mice, repeatedly over five generations, and reporting that no mice were born in consequence without a tail or even with a shorter tail. He stated that "901 young were produced by five generations of artificially mutilated parents, and yet there was not a single example of a rudimentary tail or of any other abnormality in this organ."[19]

However, the experiment has been questioned in relationship to Lamarck's hypothesis as it did not address the use and disuse of characteristics in response to the environment. Biologist Peter Gauthier noted that:

Can Weismann's experiment be considered a case of disuse? Lamarck proposed that when an organ was not used, it slowly, and very gradually atrophied. In time, over the course of many generations, it would gradually disappear as it was inherited in its modified form in each successive generation. Cutting the tails off mice does not seem to meet the qualifications of disuse, but rather falls in a category of accidental misuse... Lamarck's hypothesis has never been proven experimentally and there is no known mechanism to support the idea that somatic change, however acquired, can in some way induce a change in the germplasm. On the other hand it is difficult to disprove Lamarck's idea experimentally, and it seems that Weismann's experiment fails to provide the evidence to deny the Lamarckian hypothesis, since it lacks a key factor, namely the willful exertion of the animal in overcoming environmental obstacles.[20]

Science historian Michael Ghiselin also considers the Weismann tail-chopping experiment to have no bearing on the Lamarckian hypothesis:

The acquired characteristics that figured in Lamarck's thinking were changes that resulted from an individual's own drives and actions, not from the actions of external agents. Lamarck was not concerned with wounds, injuries or mutilations, and nothing that Lamarck had set forth was tested or "disproven" by the Weismann tail-chopping experiment.[17]

The period of the history of evolutionary thought between Darwin's death in the 1880s, and the foundation of population genetics in the 1920s and beginnings of modern evolutionary synthesis in the 1930s, is called the eclipse of Darwinism by some historians of science. During that time many scientists and philosophers accepted the reality of evolution but doubted whether natural selection was the main evolutionary mechanism.[21]

Among the most popular alternatives were theories involving the inheritance of characteristics acquired during an organism's lifetime. Scientists who felt that such Lamarckian mechanisms were the key to evolution were called neo-Lamarckians and included the British botanist George Henslow (18351925), who studied the effects of environmental stress on the growth of plants, in the belief that such environmentally-induced variation might explain much of plant evolution, and the American entomologist Alpheus Spring Packard, Jr., who studied blind animals living in caves and wrote a book in 1901 about Lamarck and his work.[22][23]

Also included were a number of paleontologists like Edward Drinker Cope and Alpheus Hyatt, who felt that the fossil record showed orderly, almost linear, patterns of development that they felt were better explained by Lamarckian mechanisms than by natural selection. Some people, including Cope and the Darwin critic Samuel Butler, felt that inheritance of acquired characteristics would let organisms shape their own evolution, since organisms that acquired new habits would change the use patterns of their organs, which would kick-start Lamarckian evolution. They considered this philosophically superior to Darwin's mechanism of random variation acted on by selective pressures. Lamarckism also appealed to those, like the philosopher Herbert Spencer and the German anatomist Ernst Haeckel, who saw evolution as an inherently progressive process.[22] The German zoologist Theodor Eimer combined Larmarckism with ideas about orthogenesis.[24]

With the development of the modern synthesis of the theory of evolution and a lack of evidence for a mechanism for acquiring and passing on new characteristics, or even their heritability, Lamarckism largely fell from favor. Unlike neo-Darwinism, the term neo-Lamarckism refers more to a loose grouping of largely heterodox theories and mechanisms that emerged after Lamarck's time, than to any coherent body of theoretical work.

In a series of experiments from 1869 to 1891, Charles-douard Brown-Squard cut the sciatic nerve of the leg and spinal cord in the dorsal regions of guinea pigs, causing an abnormal nervous condition resembling epilepsy; these were then bred and produced epileptic offspring.[25] Although some scientists considered this evidence for Lamarckian inheritance, the experiments were not Lamarckian, as they did not address the use and disuse of characteristics in response to the environment.[26] The results from the experiment were not duplicated by other scientists.[27] One explanation for the results was that they show a transmitted disease, and not evidence for the inheritance of an acquired characteristic.[28] Brown-Squard's experiments are now considered anomalous and alternative explanations have been suggested.[29]

The French botanist Gaston Bonnier, conducting experiments in the French Alps in 1884 and the Pyrenees in 1886, studied structural changes induced by growing plants at various altitudes and transplanting them to others. Bonnier believed he had proven acquired adaptive characteristics; however, he did not weed, cultivate, fertilize or protect his plant specimens from native vegetation. In the 1920s his experiments were analysed and attributed to genetic contamination rather than Lamarckian inheritance.[30]

In a series of experiments (in 1891, 1893 and 1895) on the action of light on the coloration of flatfish, the British marine biologist Joseph Thomas Cunningham (18591935) directed light upon the lower sides of flatfishes by means of a glass-bottomed tank placed over a mirror. He discovered the influence of light in producing pigments on the lower sides of flatfishes and gave his results a Lamarckian interpretation.[31][32][33] Other scientists wrote that Cunningham had received some definite results, but that they were open to more than one interpretation.[34] The geneticist William Bateson was not convinced that the cause of the increase in pigmentation was from the illumination. George Romanes wrote approvingly of Cunningham's interpretation.[35]Thomas Hunt Morgan criticized the experiments and did not believe the results were evidence for Lamarckism.[36]

In 1906, the philosopher Eugenio Rignano wrote a book, Sur La Transmissibilit Des Caractres Acquis, that argued for the inheritance of acquired characteristics.[37] He advanced a moderated Lamarckian hypothesis of inheritance known as "centro-epigenesis."[38][39] However, his views were controversial and not accepted by the majority in the scientific community.[40]

In a series of experiments from 1907 to 1910, William Lawrence Tower performed experiments on potato beetles which were said by Ernest MacBride to have provided evidence for the inheritance of acquired characteristics.[41] These were heavily criticized by William Bateson.[42] It was later suggested that his research may have been faked.[43] Tower claimed that the records of his experimental results had been lost in a fire.[44] The geneticist William E. Castle who visited Tower's laboratory was not impressed by the experimental conditions. He later concluded that Tower had faked his data. Castle found the fire suspicious and also Tower's claim that a steam leak in his greenhouse had destroyed all his beetle stocks.[45]

Experiments conducted by Gustav Tornier from 1907 to 1918 on goldfish and embryos of frogs and newts were supported by neo-Lamarckians such as Cunningham and MacBride as demonstrating the inheritance of acquired characteristics.[46][47] The abnormalities were interpreted as the result of an osmotic effect by other researchers.[48]

In the late 19th century, Frederick Merrifield exposed caterpillars and chrysalids to significantly high and low temperatures, and discovered permanent changes in some offspring's wing patterns. Swiss biologist Maximilian Rudolph Standfuss (18541917) led 30 years of intensive breeding experiments with European butterflies and after several generations, found similar preserved variations even generations after the cessation of exposing them to low temperatures.[49] Standfuss was a neo-Lamarckian and attributed the results of his experiments as direct changes to the environment.[50] In 1940, Richard Goldschmidt interpreted these results without invoking Lamarckian inheritance, and in 1998 Ernst Mayr wrote that results reported by Standfuss and others on the effects of abnormal temperatures on Lepidoptera are difficult to interpret.[51]

In 1910, the American zoologist Charles Rupert Stockard (18791939) tested the effects of alcohol intoxication on the offspring of pregnant guinea pigs. Stockard discovered that repeated alcohol intoxication in the guinea pigs produced defects and malformations in their offspring that was passed down to two or more generations. His results were challenged by the biologist Raymond Pearl who performed the same experiments with chickens.[52] Pearl discovered that the offspring of the chickens that had been exposed to alcohol were not defected but were healthy. He attributed his findings to the detrimental effects of alcohol only on the eggs and sperm which were already weak, the strong eggs and sperm were unaffected by alcohol intoxication. Pearl argued that his results had a Darwinian, not a Lamarckian explanation.[52]

The French zoologist Yves Delage in his book The Theories of Evolution (1912) reviewed experiments into Lamarckism concluded the evidence "is not of uniform value and is more or less open to criticism; very little of it is convincing... [due to] difficulties of experimentation and, above all, of interpretation."[53]

In a series of experiments, Francis Bertody Sumner (18741945) reared several generations of white mice under different conditions of temperature and relative humidity.[54] Sumner discovered that the white mice at 20C to 30C developed longer bodies, tails and hind feet which were also transmitted to their offspring over a number of generations, however, later results were not entirely consistent and the experiments ended in uncertainty.[55]

Between 1918 and 1924, two American scientists Michael F. Guyer and Elizabeth A. Smith performed experiments in which fowl serum antibodies for rabbit lens-protein were injected into pregnant rabbits which resulted in defects in the eyes of some of their offspring that were inherited through eight generations.[56] Their experiments were criticized and were not repeated by other scientists.[57]

In the 1920s, experiments by Paul Kammerer on amphibians, particularly the midwife toad, appeared to find evidence supporting Lamarckism. However, his specimens with supposedly acquired black foot-pads were found to have been tampered with. In The Case of the Midwife Toad (1971), author and journalist Arthur Koestler surmised that the tampering had been done by a Nazi sympathiser to discredit Kammerer for his political views, and that his research might actually have been valid. However, most biologists believe that Kammerer was a fraud, and even among those who believe he was honest, most believe that he misinterpreted the results of his experiments.[58]

During the 1920s, Harvard University researcher William McDougall studied the abilities of rats to correctly solve mazes. He found that offspring of rats that had learned the maze were able to run it faster. The first rats would get it wrong 165 times before being able to run it perfectly each time, but after a few generations it was down to 20. McDougall attributed this to some sort of Lamarckian evolutionary process.[59]Oscar Werner Tiegs and Wilfred Eade Agar later showed McDougall's results to be incorrect, caused by poor experimental controls.[60][61]Peter Medawar wrote that "careful and extensive repetitions of McDougall's research failed altogether to confirm it. His work therefore becomes an exhibit in the capacious ill-lit museum of unreproducible phenomena."[62]

In the 1920s, John William Heslop-Harrison conducted experiments on the peppered moth, claiming to have evidence for the inheritance of acquired characteristics. Other scientists failed to replicate his results.[63][64] The Russian physiologist Ivan Pavlov claimed to have observed a similar phenomenon in white mice being subject to a conditioned reflex experiment involving food and the sound of a bell. He wrote that with each generation, the mice became easier to condition. In 1926, Pavlov announced that there had been a fatal flaw in his experiment and retracted his claim to have demonstrated Lamarckian inheritance.[65] Other researchers were also unable to replicate his results.[66]

In other experiments, Coleman Griffith (1920, 1922) and John Detlefson (1923, 1925) reared rats in cages on a rotating table for three months. The rats adapted to the rotating condition to such an extent that when the rotation was stopped they showed signs of disequilibration and other physiological conditions which were inherited for several generations.[67][68][69][70] In 1933, Roy Dorcus replicated their experiments but obtained different results as the rotated rats did not manifest any abnormalities of posture described by Griffith and Detlefson.[71] Other studies revealed that the same abnormalities could occur in rats without rotation if they were suffering from an ear infection thus the results were interpreted as a case of infection, not Lamarckian inheritance.[72]

In the 1930s, the German geneticist Victor Jollos (18871941) in a series of experiments claimed evidence for inherited changes induced by heat treatment in Drosophila melanogaster.[73] His experiments were described as Lamarckian. However, Jollos was not an advocate of Lamarckian evolution and attributed the results from his experiments as evidence for directed mutagenesis. American scientists were unable to replicate his results.[74]

The British anthropologist Frederic Wood Jones and the South African paleontologist Robert Broom supported a neo-Lamarckian view of human evolution as opposed to the Darwinian view. The German anthropologist Hermann Klaatsch relied on a neo-Lamarckian model of evolution to try and explain the origin of bipedalism. Neo-Lamarckism remained influential in biology until the 1940s when the role of natural selection was reasserted in evolution as part of the modern evolutionary synthesis.[75]

Herbert Graham Cannon, a British zoologist, defended Lamarckism in his 1959 book Lamarck and Modern Genetics.[76]

In the 1960s, "biochemical Lamarckism" was advocated by the embryologist Paul Wintrebert.[77]

In the 1970s, Australian immunologist Edward J. Steele and colleagues proposed a neo-Lamarckian mechanism to try to explain why homologous DNA sequences from the VDJ gene regions of parent mice were found in their germ cells and seemed to persist in the offspring for a few generations. The mechanism involved the somatic selection and clonal amplification of newly acquired antibody gene sequences that were generated via somatic hypermutation in B-cells. The messenger RNA (mRNA) products of these somatically novel genes were captured by retroviruses endogenous to the B-cells and were then transported through the bloodstream where they could breach the soma-germ barrier and retrofect (reverse transcribe) the newly acquired genes into the cells of the germ line. Although Steele was advocating this theory for the better part of two decades, little more than indirect evidence was ever acquired to support it. An interesting attribute of this idea is that it strongly resembles Darwin's own theory of pangenesis, except in the soma to germ line feedback theory, pangenes are replaced with realistic retroviruses.[78] Regarding Steele's research, historian of biology Peter J. Bowler wrote, "his work was bitterly criticized at the time by biologists who doubted his experimental results and rejected his hypothetical mechanism as implausible."[79]

Neo-Lamarckism was dominant in French biology for more than a century. French scientists who supported neo-Lamarckism included Edmond Perrier (18441921), Alfred Giard (18461908), Gaston Bonnier (18531922) and Pierre-Paul Grass (18951985).[80]

In 1987, Ryuichi Matsuda coined the term "pan-environmentalism" for his evolutionary theory which he saw as a fusion of Darwinism with neo-Lamarckism. He held that heterochrony is a main mechanism for evolutionary change and that novelty in evolution can be generated by genetic assimilation.[81][82] His views were criticized by Arthur M. Shapiro for providing no solid evidence for his theory. Shapiro noted that "Matsuda himself accepts too much at face value and is prone to wish-fulfilling interpretation."[82]

Within the discipline of history of technology, Lamarckism has been used in linking cultural development to human evolution by classifying artefacts as extensions of human anatomy: in other words, as the acquired cultural characteristics of human beings. Ben Cullen has shown that a strong element of Lamarckism exists in sociocultural evolution.[83]

A form of Lamarckism was revived in the Soviet Union of the 1930s when Trofim Lysenko promoted Lysenkoism which suited the ideological opposition of Joseph Stalin to genetics. This ideologically driven research influenced Soviet agricultural policy which in turn was later blamed for crop failures.[84]

Neo-Lamarckian versions of evolution were widespread in the late 19th century. The idea that living things could to some degree choose the characteristics that would be inherited allowed them things to be in charge of their own destiny as opposed to the Darwinian view, which made them puppets at the mercy of the environment. Such ideas were more popular than natural selection in the late 19th century as it made it possible for biological evolution to fit into a framework of a divine or naturally willed plan, thus the neo-Lamarckian view of evolution was often advocated by proponents of orthogenesis.[85] According to Peter J. Bowler:

One of the most emotionally compelling arguments used by the neo-Lamarckians of the late nineteenth century was the claim that Darwinism was a mechanistic theory which reduced living things to puppets driven by heredity. The selection theory made life into a game of Russian roulette, where life or death was predetermined by the genes one inherited. The individual could do nothing to mitigate bad heredity. Lamarckism, in contrast, allowed the individual to choose a new habit when faced with an environmental challenge and shape the whole future course of evolution.[86]

Supporters of neo-Lamarckism such as George Bernard Shaw and Arthur Koestler claimed that Lamarckism is more humane and optimistic than Darwinism.[87]

George Gaylord Simpson in his book Tempo and Mode in Evolution (1944) claimed that experiments in heredity have failed to corroborate any Lamarckian process.[88] Simpson noted that neo-Lamarckism "stresses a factor that Lamarck rejected: inheritance of direct effects of the environment" and neo-Lamarckism is closer to Darwin's pangenesis than Lamarck's views.[89] Simpson wrote, "the inheritance of acquired characters, failed to meet the tests of observation and has been almost universally discarded by biologists."[90]

Botanist Conway Zirkle pointed out that Lamarck did not originate the hypothesis that acquired characters were heritable, therefore it is incorrect to refer to it as Lamarckism:

What Lamarck really did was to accept the hypothesis that acquired characters were heritable, a notion which had been held almost universally for well over two thousand years and which his contemporaries accepted as a matter of course, and to assume that the results of such inheritance were cumulative from generation to generation, thus producing, in time, new species. His individual contribution to biological theory consisted in his application to the problem of the origin of species of the view that acquired characters were inherited and in showing that evolution could be inferred logically from the accepted biological hypotheses. He would doubtless have been greatly astonished to learn that a belief in the inheritance of acquired characters is now labeled "Lamarckian," although he would almost certainly have felt flattered if evolution itself had been so designated.[91]

Peter Medawar wrote regarding Lamarckism, "very few professional biologists believe that anything of the kind occursor can occurbut the notion persists for a variety of nonscientific reasons." Medawar stated there is no known mechanism by which an adaption acquired in an individual's lifetime can be imprinted on the genome and Lamarckian inheritance is not valid unless it excludes the possibility of natural selection but this has not been demonstrated in any experiment.[92]

Martin Gardner wrote in his book Fads and Fallacies in the Name of Science (1957):

A host of experiments have been designed to test Lamarckianism. All that have been verified have proved negative. On the other hand, tens of thousands of experiments reported in the journals and carefully checked and rechecked by geneticists throughout the world have established the correctness of the gene-mutation theory beyond all reasonable doubt... In spite of the rapidly increasing evidence for natural selection, Lamarck has never ceased to have loyal followers.... There is indeed a strong emotional appeal in the thought that every little effort an animal puts forth is somehow transmitted to his progeny.[93]

According to Ernst Mayr, any Lamarckian theory involving the inheritance of acquired characters has been refuted as "DNA does not directly participate in the making of the phenotype and that the phenotype, in turn, does not control the composition of the DNA."[94] Peter J. Bowler has written that although many early scientists took Lamarckism seriously, it was discredited by genetics in the early twentieth century.[95]

Forms of 'soft' or epigenetic inheritance within organisms have been suggested as neo-Lamarckian in nature by such scientists as Eva Jablonka and Marion J. Lamb. In addition to 'hard' or genetic inheritance, involving the duplication of genetic material and its segregation during meiosis, there are other hereditary elements that pass into the germ cells also.[96] These include things like methylation patterns in DNA and chromatin marks, both of which regulate the activity of genes. These are considered Lamarckian in the sense that they are responsive to environmental stimuli and can differentially affect gene expression adaptively, with phenotypic results that can persist for many generations in certain organisms.[97]

Jablonka and Lamb have called for an extended evolutionary synthesis. They have argued that there is evidence for Lamarckian epigenetic control systems causing evolutionary changes and the mechanisms underlying epigenetic inheritance can also lead to saltational changes that reorganize the epigenome.[98]

Interest in Lamarckism has increased, as studies in the field of epigenetics have highlighted the possible inheritance of behavioral traits acquired by the previous generation.[96] A 2009 study examined foraging behavior in chickens as a function of stress:

Transmissions of information across generations which does not involve traditional inheritance of DNA-sequence alleles is often referred to as soft inheritance [99] or "Lamarckian inheritance."[100]

The study concluded:

Our findings suggest that unpredictable food access caused seemingly adaptive responses in feeding behavior, which may have been transmitted to the offspring by means of epigenetic mechanisms, including regulation of immune genes. This may have prepared the offspring for coping with an unpredictable environment.[100]

The evolution of acquired characteristics has also been shown in human populations who have experienced starvation, resulting in altered gene function in both the starved population and their offspring.[101] The process of DNA methylation is thought to be behind such changes.

In October 2010, further evidence linking food intake to traits inherited by the offspring were shown in a study of rats conducted by several Australian universities.[102] The study strongly suggested that fathers can transfer a propensity for obesity to their daughters as a result of the fathers' food intake, and not their genetics (or specific genes), prior to the conception of the daughter. A "paternal high-fat diet" was shown to cause cell dysfunction in the daughter, which in turn led to obesity for the daughter. Felicia Nowak, et al. reported at the Endocrine Society meeting in June 2013 that obese male rats passed on the tendency to obesity to their male offspring.[103]

Several studies, one conducted by researchers at Massachusetts Institute of Technology and another by researchers at the Tufts University School of Medicine, have rekindled the debate once again. As reported in MIT Technology Review in February 2009, "The effects of an animal's environment during adolescence can be passed down to future offspring ... The findings provide support for a 200-year-old theory of evolution that has been largely dismissed: Lamarckian evolution, which states that acquired characteristics can be passed on to offspring."[104] A report investigating the inheritance of resistance to viral infection in the nematode Caenorhabditis elegans suggests that small RNA molecules may be inherited in a non-Mendelian fashion and provide resistance to infection.[105] More recent studies in C. elegans have revealed that progeny may inherit information regarding environmental challenges that the parent experienced, such as starvation, and that this epigenetic effect may persist for multiple generations.[106]

A study (Akimoto et al. 2007) on epigenetic inheritance in rice plants came to the conclusion that "gene expression is flexibly tuned by methylation, allowing plants to gain or lose particular traits which are heritable as far as methylation patterns of corresponding genes are maintained. This is in support of the concept of Lamarckian inheritance, suggesting that acquired traits are heritable."[107] Another study (Sano, 2010) wrote that observations suggest that acquired traits are heritable in plants as far as the acquired methylation pattern is stably transmitted which is consistent with Lamarckian evolution.[108] Handel and Ramagopalan found that there is evidence that epigenetic alterations such as DNA methylation and histone modifications are transmitted transgenerationally as a mechanism for environmental influences to be passed from parents to offspring. According to Handel and Romagopalan "epigenetics allows the peaceful co-existence of Darwinian and Lamarckian evolution."[109]

In their book An Introduction to Zoology (2013), Joseph Springer and Dennis Holley wrote:

Lamarck and his ideas were ridiculed and discredited. In a strange twist of fate, Lamarck may have the last laugh. Epigenetics, an emerging field of genetics, has shown that Lamarck may have been at least partially correct all along. It seems that reversible and heritable changes can occur without a change in DNA sequence (genotype) and that such changes may be induced spontaneously or in response to environmental factorsLamarck's "acquired traits." Determining which observed phenotypes are genetically inherited and which are environmentally induced remains an important and ongoing part of the study of genetics, developmental biology, and medicine.[110]

Eugene Koonin has written that the prokaryotic CRISPR system and Piwi-interacting RNA could be classified as Lamarckian and came to the conclusion that "Both Darwinian and Lamarckian modalities of evolution appear to be important, and reflect different aspects of the interaction between populations and the environment."[111]

A study in 2013 reported that mutations caused by a father's lifestyle can be inherited by his children through multiple generations.[112] A study from Lund University in Sweden showed that exercise changes the epigenetic pattern of genes that affect fat storage in the body.[113]

Commenting on this, Charlotte Ling explained:

The cells of the body contain DNA, which contains genes. We inherit our genes and they cannot be changed. The genes, however, have 'methyl groups' attached which affect what is known as 'gene expression' whether the genes are activated or deactivated. The methyl groups can be influenced in various ways, through exercise, diet and lifestyle, in a process known as 'DNA methylation'.[114]

A 2013 study published in Nature Neuroscience reported that mice trained to fear the smell of a chemical called acetophenone passed their fear onto at least two generations.[115][116] The science magazine New Scientist commented on the study saying, "While it needs to be corroborated, this finding seems consistent with Lamarckian inheritance. It is, however, based on epigenetics: changes that tweak the action of genes, not the genes themselves. So it fits with natural selection and may yet give Lamarck's name a sheen of respectability."[117]

Guy Barry wrote that Darwin's hypothesis pangenesis coupled with "Lamarckian somatic cell-derived epigenetic modifications" and de novo RNA and DNA mutations can explain the evolution of the human brain.[118]

Lamarckian elements also appear in the hologenome theory of evolution.[119]

The significance of epigenetic inheritance to the evolutionary process is uncertain. Critics assert that epigenetic inheritance modifications are not inherited past two or three generations, so are not a stable basis for evolutionary change.[122][123] According to a recent review in 2015, "there are no reported epigenetic marks transmitted via the male germ line during more than three generations."[122]

The evolutionary biologist T. Ryan Gregory contends that epigenetic inheritance should not be considered Lamarckian. According to Gregory, Lamarck did not claim the environment imposed direct effects on organisms. Instead, Lamarck "argued that the environment created needs to which organisms responded by using some features more and others less, that this resulted in those features being accentuated or attenuated, and that this difference was then inherited by offspring." Gregory has stated that Lamarckian evolution in the context of epigenetics is actually closer to the view held by Darwin rather than by Lamarck.[6]

In a paper titled Weismann Rules! OK? Epigenetics and the Lamarckian Temptation (2007), David Haig writes that research into epigenetic processes does allow a Lamarckian element in evolution but the processes do not challenge the main tenets of the modern evolutionary synthesis as modern Lamarckians have claimed. Haig argued for the primary of DNA and evolution of epigenetic switches by natural selection.[124] Haig has also written there is a "visceral attraction" to Lamarckian evolution from the public and some scientists as it posits the world with a meaning, in which organisms can shape their own evolutionary destiny.[125]

American biologist Jerry Coyne has stated that "lots of studies show us that Lamarckian inheritance doesnt operate" and epigenetic changes are rarely passed on to future generations, thus do not serve as the basis of evolutionary change.[126] Coyne has also written:

Lamarckism is not a heresy, but simply a hypothesis that hasnt held up... If epigenetics in the second sense is so important in evolution, let us have a list of, say, a hundred adaptations of organisms that evolved in this Larmackian way as opposed to the old, boring, neo-Darwinian way involving inherited changes in DNA sequence... I cant think of a single entry for that list.[127]

Thomas Dickens and Qazi Rahman (2012) have written epigenetic mechanisms such as DNA methylation and histone modification are genetically inherited under the control of natural selection and do not challenge the modern synthesis. Dickens and Rahman have taken issue with the claims of Eva Jablonka and Marion J. Lamb on Lamarckian epigenetic processes.[128]

Edith Heard and Robert Martienssen (2014) in a Cell review were not convinced that epigenetics has revived Lamarckism as there is no evidence epigenetic changes are passed on to successive generations in mammals. They concluded the characteristics that are thought to be the result of epigenetic inheritance may be caused by other factors such as behavioral changes, undetected mutations, microbiome alterations or the transmission of metabolites.[129]

In 2015, Khursheed Iqbal and colleagues discovered that although "endocrine disruptors exert direct epigenetic effects in the exposed fetal germ cells, these are corrected by reprogramming events in the next generation." Molecular biologist Emma Whitelaw has cited this study as an example of evidence disputing Lamarckian epigenetic inheritance.[130] Another critic recently argued that bringing back Lamarck in the context of epigenetics is misleading, commenting, "We should remember [Lamarck] for the good he contributed to science, not for things that resemble his theory only superficially. Indeed, thinking of CRISPR and other phenomena as Lamarckian only obscures the simple and elegant way evolution really works."[131]

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Drosophila melanogaster – Wikipedia

Sunday, December 25th, 2016

Drosophila melanogaster is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting with Charles W. Woodworth's proposal of the use of this species as a model organism, D. melanogaster continues to be widely used for biological research in studies of genetics, physiology, microbial pathogenesis, and life history evolution. It is typically used because it is an animal species that is easy to care for, has four pairs of chromosomes, breeds quickly, and lays many eggs.[2]D. melanogaster is a common pest in homes, restaurants, and other occupied places where food is served.[3]

Flies belonging to the family Tephritidae are also called "fruit flies". This can cause confusion, especially in Australia and South Africa, where the Mediterranean fruit fly Ceratitis capitata is an economic pest.

Wildtype fruit flies are yellow-brown, with brick-red eyes and transverse black rings across the abdomen. They exhibit sexual dimorphism: females are about 2.5 millimeters (0.098in) long; males are slightly smaller with darker backs. Males are easily distinguished from females based on colour differences, with a distinct black patch at the abdomen, less noticeable in recently emerged flies (see fig.), and the sexcombs (a row of dark bristles on the tarsus of the first leg). Furthermore, males have a cluster of spiky hairs (claspers) surrounding the reproducing parts used to attach to the female during mating. There are extensive images at FlyBase.[4]

Egg of D. melanogaster

The D. melanogaster lifespan is about 30 days at 29C (84F).

The developmental period for D. melanogaster varies with temperature, as with many ectothermic species. The shortest development time (egg to adult), 7 days, is achieved at 28C (82F).[5][6] Development times increase at higher temperatures (11 days at 30C or 86F) due to heat stress. Under ideal conditions, the development time at 25C (77F) is 8.5 days,[5][6][7] at 18C (64F) it takes 19 days[5][6] and at 12C (54F) it takes over 50 days.[5][6] Under crowded conditions, development time increases,[8] while the emerging flies are smaller.[8][9] Females lay some 400 eggs (embryos), about five at a time, into rotting fruit or other suitable material such as decaying mushrooms and sap fluxes. The eggs, which are about 0.5mm long, hatch after 1215 hours (at 25C or 77F).[5][6] The resulting larvae grow for about 4 days (at 25C) while molting twice (into second- and third-instar larvae), at about 24 and 48 h after hatching.[5][6] During this time, they feed on the microorganisms that decompose the fruit, as well as on the sugar of the fruit itself. The mother puts feces on the egg sacs to establish the same microbial composition in the larvae's guts which has worked positively for herself.[10] Then the larvae encapsulate in the puparium and undergo a four-day-long metamorphosis (at 25C), after which the adults eclose (emerge).[5][6]

Females become receptive to courting males at about 812 hours after emergence.[11] Specific neuron groups in females have been found to affect copulation behavior and mate choice. One such group in the abdominal nerve cord allows the female fly to pause her body movements to copulate.[12] Activation of these neurons induces the female to cease movement and orient herself towards the male to allow for mounting. If the group is inactivated, the female remains in motion and does not copulate. Various chemical signals such as male pheromones often are able to activate the group.[12]

The female fruit fly prefers a shorter duration when it comes to sex. Males, on the other hand, prefer it to last longer.[13] Males perform a sequence of five behavioral patterns to court females. First, males orient themselves while playing a courtship song by horizontally extending and vibrating their wings. Soon after, the male positions itself at the rear of the female's abdomen in a low posture to tap and lick the female genitalia. Finally, the male curls its abdomen and attempts copulation. Females can reject males by moving away, kicking, and extruding their ovipositor.[14] Copulation lasts around 1520 minutes,[15] during which males transfer a few hundred, very long (1.76mm) sperm cells in seminal fluid to the female.[16] Females store the sperm in a tubular receptacle and in two mushroom-shaped spermathecae; sperm from multiple matings compete for fertilization. A last male precedence is believed to exist in which the last male to mate with a female sires about 80% of her offspring. This precedence was found to occur through both displacement and incapacitation.[17] The displacement is attributed to sperm handling by the female fly as multiple matings are conducted and is most significant during the first 12 days after copulation. Displacement from the seminal receptacle is more significant than displacement from the spermathecae.[17] Incapacitation of first male sperm by second male sperm becomes significant 27 days after copulation. The seminal fluid of the second male is believed to be responsible for this incapacitation mechanism (without removal of first male sperm) which takes effect before fertilization occurs.[17] The delay in effectiveness of the incapacitation mechanism is believed to be a protective mechanism that prevents a male fly from incapacitating its own sperm should it mate with the same female fly repetitively. Sensory neurons in the uterus of female D. melanogaster respond to a male protein, sex peptide, which is found in sperm.[12] This protein makes the female reluctant to copulate for about 10 days after insemination. The signal pathway leading to this change in behavior has been determined. The signal is sent to a brain region that is a homolog of the hypothalamus and the hypothalamus then controls sexual behavior and desire[12]

D. melanogaster is often used for life extension studies, such as to identify genes purported to increase lifespan when mutated.[18]

D. melanogaster females exhibit mate choice copying. When virgin females are shown other females copulating with a certain type of male, they tend to copulate more with this type of male afterwards than naive females (which have not observed the copulation of others). This behavior is sensitive to environmental conditions, and females copy less in bad weather conditions.[19]

D. melanogaster males exhibit a strong reproductive learning curve. That is, with sexual experience, these flies tend to modify their future mating behavior in multiple ways. These changes include increased selectivity for courting only intraspecifically, as well as decreased courtship times.

Sexually nave D. melanogaster males are known to spend significant time courting interspecifically, such as with D. simulans flies. Nave D. melanogaster will also attempt to court females that are not yet sexually mature, and other males. D. melanogaster males show little to no preference for D. melanogaster females over females of other species or even other male flies. However, after D. simulans or other flies incapable of copulation have rejected the males advances, D. melanogaster males are much less likely to spend time courting nonspecifically in the future. This apparent learned behavior modification seems to be evolutionarily significant, as it allows the males to avoid investing energy into futile sexual encounters.[20]

In addition, males with previous sexual experience will modify their courtship dance when attempting to mate with new females the experienced males spend less time courting and therefore have lower mating latencies, meaning that they are able to reproduce more quickly. This decreased mating latency leads to a greater mating efficiency for experienced males over nave males.[21] This modification also appears to have obvious evolutionary advantages, as increased mating efficiency is extremely important in the eyes of natural selection.

Both male and female D. melanogaster act polygamously (having multiple sexual partners at the same time).[22] In both males and females, polygamy results in a decrease in evening activity compared to virgin flies, more so in males than females.[22] Evening activity consists of the activities that the flies participate in other than mating and finding partners, such as finding food.[23] The reproductive success of males and females varies, due to the fact that a female only needs to mate once to reach maximum fertility.[23] Mating with multiple partners provides no advantage over mating with one partner, and therefore females exhibit no difference in evening activity between polygamous and monogamous individuals.[23] For males, however, mating with multiple partners increases their reproductive success by increasing the genetic diversity of their offspring.[23] This benefit of genetic diversity is an evolutionary advantage because it increases the chance that some of the offspring will have traits that increase their fitness in their environment.

The difference in evening activity between polygamous and monogamous male flies can be explained with courtship. For polygamous flies, their reproductive success increases by having offspring with multiple partners, and therefore they spend more time and energy on courting multiple females.[23] On the other hand, monogamous flies only court one female, and expend less energy doing so.[23] While it requires more energy for male flies to court multiple females, the overall reproductive benefits it produces has kept polygamy as the preferred sexual choice.[23]

It has been shown that the mechanism that affects courtship behavior in Drosophila is controlled by the oscillator neurons DN1s and LNDs.[24] Oscillation of the DN1 neurons was found to be effected by socio-sexual interactions, and is connected to mating-related decrease of evening activity.[24]

D. melanogaster was among the first organisms used for genetic analysis, and today it is one of the most widely used and genetically best-known of all eukaryotic organisms. All organisms use common genetic systems; therefore, comprehending processes such as transcription and replication in fruit flies helps in understanding these processes in other eukaryotes, including humans.[25]

Thomas Hunt Morgan began using fruit flies in experimental studies of heredity at Columbia University in 1910 in a laboratory known as the Fly Room. The Fly Room was cramped with eight desks, each occupied by students and their experiments. They started off experiments using milk bottles to rear the fruit flies and handheld lenses for observing their traits. The lenses were later replaced by microscopes, which enhanced their observations. Morgan and his students eventually elucidated many basic principles of heredity, including sex-linked inheritance, epistasis, multiple alleles, and gene mapping.[25]

D. melanogaster is one of the most studied organisms in biological research, particularly in genetics and developmental biology. The several reasons include:

Genetic markers are commonly used in Drosophila research, for example within balancer chromosomes or P-element inserts, and most phenotypes are easily identifiable either with the naked eye or under a microscope. In the list of example common markers below, the allele symbol is followed by the name of the gene affected and a description of its phenotype. (Note: Recessive alleles are in lower case, while dominant alleles are capitalised.)

Drosophila genes are traditionally named after the phenotype they cause when mutated. For example, the absence of a particular gene in Drosophila will result in a mutant embryo that does not develop a heart. Scientists have thus called this gene tinman, named after the Oz character of the same name.[27] This system of nomenclature results in a wider range of gene names than in other organisms.

The genome of D. melanogaster (sequenced in 2000, and curated at the FlyBase database[26]) contains four pairs of chromosomes: an X/Y pair, and three autosomes labeled 2, 3, and 4. The fourth chromosome is so tiny, it is often ignored, aside from its important eyeless gene. The D. melanogaster sequenced genome of 139.5 million base pairs has been annotated[28] and contains around 15,682 genes according to Ensemble release 73. More than 60% of the genome appears to be functional non-protein-coding DNA[29] involved in gene expression control. Determination of sex in Drosophila occurs by the X:A ratio of X chromosomes to autosomes, not because of the presence of a Y chromosome as in human sex determination. Although the Y chromosome is entirely heterochromatic, it contains at least 16 genes, many of which are thought to have male-related functions.[30]

A March 2000 study by National Human Genome Research Institute comparing the fruit fly and human genome estimated that about 60% of genes are conserved between the two species.[31] About 75% of known human disease genes have a recognizable match in the genome of fruit flies,[32] and 50% of fly protein sequences have mammalian homologs. An online database called Homophila is available to search for human disease gene homologues in flies and vice versa.[33]Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. The fly is also being used to study mechanisms underlying aging and oxidative stress, immunity, diabetes, and cancer, as well as drug abuse.

Embryogenesis in Drosophila has been extensively studied, as its small size, short generation time, and large brood size makes it ideal for genetic studies. It is also unique among model organisms in that cleavage occurs in a syncytium.

During oogenesis, cytoplasmic bridges called "ring canals" connect the forming oocyte to nurse cells. Nutrients and developmental control molecules move from the nurse cells into the oocyte. In the figure to the left, the forming oocyte can be seen to be covered by follicular support cells.

After fertilization of the oocyte, the early embryo (or syncytial embryo) undergoes rapid DNA replication and 13 nuclear divisions until about 5000 to 6000 nuclei accumulate in the unseparated cytoplasm of the embryo. By the end of the eighth division, most nuclei have migrated to the surface, surrounding the yolk sac (leaving behind only a few nuclei, which will become the yolk nuclei). After the 10th division, the pole cells form at the posterior end of the embryo, segregating the germ line from the syncytium. Finally, after the 13th division, cell membranes slowly invaginate, dividing the syncytium into individual somatic cells. Once this process is completed, gastrulation starts.[34]

Nuclear division in the early Drosophila embryo happens so quickly, no proper checkpoints exist, so mistakes may be made in division of the DNA. To get around this problem, the nuclei that have made a mistake detach from their centrosomes and fall into the centre of the embryo (yolk sac), which will not form part of the fly.

The gene network (transcriptional and protein interactions) governing the early development of the fruit fly embryo is one of the best understood gene networks to date, especially the patterning along the anteroposterior (AP) and dorsoventral (DV) axes (See under morphogenesis).[34]

The embryo undergoes well-characterized morphogenetic movements during gastrulation and early development, including germ-band extension, formation of several furrows, ventral invagination of the mesoderm, and posterior and anterior invagination of endoderm (gut), as well as extensive body segmentation until finally hatching from the surrounding cuticle into a first-instar larva.

During larval development, tissues known as imaginal discs grow inside the larva. Imaginal discs develop to form most structures of the adult body, such as the head, legs, wings, thorax, and genitalia. Cells of the imaginal disks are set aside during embryogenesis and continue to grow and divide during the larval stagesunlike most other cells of the larva, which have differentiated to perform specialized functions and grow without further cell division. At metamorphosis, the larva forms a pupa, inside which the larval tissues are reabsorbed and the imaginal tissues undergo extensive morphogenetic movements to form adult structures.

Drosophila flies have both X and Y chromosomes, as well as autosomes. Unlike humans, the Y chromosome does not confer maleness; rather, it encodes genes necessary for making sperm. Sex is instead determined by the ratio of X chromosomes to autosomes. Furthermore, each cell "decides" whether to be male or female independently of the rest of the organism, resulting in the occasional occurrence of gynandromorphs.

Three major genes are involved in determination of Drosophila sex. These are sex-lethal, sisterless, and deadpan. Deadpan is an autosomal gene which inhibits sex-lethal, while sisterless is carried on the X chromosome and inhibits the action of deadpan. An AAX cell has twice as much deadpan as sisterless, so sex-lethal will be inhibited, creating a male. However, an AAXX cell will produce enough sisterless to inhibit the action of deadpan, allowing the sex-lethal gene to be transcribed to create a female.

Later, control by deadpan and sisterless disappears and what becomes important is the form of the sex-lethal gene. A secondary promoter causes transcription in both males and females. Analysis of the cDNA has shown that different forms are expressed in males and females. Sex-lethal has been shown to affect the splicing of its own mRNA. In males, the third exon is included which encodes a stop codon, causing a truncated form to be produced. In the female version, the presence of sex-lethal causes this exon to be missed out; the other seven amino acids are produced as a full peptide chain, again giving a difference between males and females.[35]

Presence or absence of functional sex-lethal proteins now go on to affect the transcription of another protein known as doublesex. In the absence of sex-lethal, doublesex will have the fourth exon removed and be translated up to and including exon 6 (DSX-M[ale]), while in its presence the fourth exon which encodes a stop codon will produce a truncated version of the protein (DSX-F[emale]). DSX-F causes transcription of Yolk proteins 1 and 2 in somatic cells, which will be pumped into the oocyte on its production.

Unlike mammals, Drosophila flies only have innate immunity and lack an adaptive immune response. The D. melanogaster immune system can be divided into two responses: humoral and cell-mediated. The former is a systemic response mediated through the Toll and imd pathways, which are parallel systems for detecting microbes. The Toll pathway in Drosophila is known as the homologue of Toll-like pathways in mammals. Spatzle, a known ligand for the Toll pathway in flies, is produced in response to Gram-positive bacteria, parasites, and fungal infection. Upon infection, pro-Spatzle will be cleaved by protease SPE (Spatzle processing enzyme) to become active Spatzle, which then binds to the Toll receptor located on the cell surface (Fat body, hemocytes) and dimerise for activation of downstream NF-B signaling pathways. The imd pathway, though, is triggered by Gram-negative bacteria through soluble and surface receptors (PGRP-LE and LC, respectively). D. melanogaster has a "fat body", which is thought to be homologous to the human liver. It is the primary secretory organ and produces antimicrobial peptides. These peptides are secreted into the hemolymph and bind infectious bacteria, killing them by forming pores in their cell walls. Years ago[when?] many drug companies wanted to purify these peptides and use them as antibiotics. Other than the fat body, hemocytes, the blood cells in Drosophila, are known as the homologue of mammalian monocyte/macrophages, possessing a significant role in immune responses. It is known from the literature that in response to immune challenge, hemocytes are able to secrete cytokines, for example Spatzle, to activate downstream signaling pathways in the fat body. However, the mechanism still remains unclear.

In 1971, Ron Konopka and Seymour Benzer published "Clock mutants of Drosophila melanogaster", a paper describing the first mutations that affected an animal's behavior. Wild-type flies show an activity rhythm with a frequency of about a day (24 hours). They found mutants with faster and slower rhythms, as well as broken rhythmsflies that move and rest in random spurts. Work over the following 30 years has shown that these mutations (and others like them) affect a group of genes and their products that comprise a biochemical or biological clock. This clock is found in a wide range of fly cells, but the clock-bearing cells that control activity are several dozen neurons in the fly's central brain.

Since then, Benzer and others have used behavioral screens to isolate genes involved in vision, olfaction, audition, learning/memory, courtship, pain, and other processes, such as longevity.

The first learning and memory mutants (dunce, rutabaga, etc.) were isolated by William "Chip" Quinn while in Benzer's lab, and were eventually shown to encode components of an intracellular signaling pathway involving cyclic AMP, protein kinase A, and a transcription factor known as CREB. These molecules were shown to be also involved in synaptic plasticity in Aplysia and mammals.[citation needed]

Male flies sing to the females during courtship using their wings to generate sound, and some of the genetics of sexual behavior have been characterized. In particular, the fruitless gene has several different splice forms, and male flies expressing female splice forms have female-like behavior and vice versa. The TRP channels nompC, nanchung, and inactive are expressed in sound-sensitive Johnston's organ neurons and participate in the transduction of sound.[36][37]

Furthermore, Drosophila has been used in neuropharmacological research, including studies of cocaine and alcohol consumption. Models for Parkinson's disease also exist for flies.[38]

Stereo images of the fly eye

The compound eye of the fruit fly contains 760 unit eyes or ommatidia, and are one of the most advanced among insects. Each ommatidium contains eight photoreceptor cells (R1-8), support cells, pigment cells, and a cornea. Wild-type flies have reddish pigment cells, which serve to absorb excess blue light so the fly is not blinded by ambient light.

Each photoreceptor cell consists of two main sections, the cell body and the rhabdomere. The cell body contains the nucleus, while the 100-m-long rhabdomere is made up of toothbrush-like stacks of membrane called microvilli. Each microvillus is 12 m in length and about 60 nm in diameter.[39] The membrane of the rhabdomere is packed with about 100 million rhodopsin molecules, the visual protein that absorbs light. The rest of the visual proteins are also tightly packed into the microvillar space, leaving little room for cytoplasm.

The photoreceptors in Drosophila express a variety of rhodopsin isoforms. The R1-R6 photoreceptor cells express rhodopsin1 (Rh1), which absorbs blue light (480nm). The R7 and R8 cells express a combination of either Rh3 or Rh4, which absorb UV light (345nm and 375nm), and Rh5 or Rh6, which absorb blue (437nm) and green (508nm) light, respectively. Each rhodopsin molecule consists of an opsin protein covalently linked to a carotenoid chromophore, 11-cis-3-hydroxyretinal.[40]

As in vertebrate vision, visual transduction in invertebrates occurs via a G protein-coupled pathway. However, in vertebrates, the G protein is transducin, while the G protein in invertebrates is Gq (dgq in Drosophila). When rhodopsin (Rh) absorbs a photon of light its chromophore, 11-cis-3-hydroxyretinal, is isomerized to all-trans-3-hydroxyretinal. Rh undergoes a conformational change into its active form, metarhodopsin. Metarhodopsin activates Gq, which in turn activates a phospholipase C (PLC) known as NorpA.[41]

PLC hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP2), a phospholipid found in the cell membrane, into soluble inositol triphosphate (IP3) and diacylglycerol (DAG), which stays in the cell membrane. DAG or a derivative of DAG causes a calcium-selective ion channel known as transient receptor potential (TRP) to open and calcium and sodium flows into the cell. IP3 is thought to bind to IP3 receptors in the subrhabdomeric cisternae, an extension of the endoplasmic reticulum, and cause release of calcium, but this process does not seem to be essential for normal vision.[41]

Calcium binds to proteins such as calmodulin (CaM) and an eye-specific protein kinase C (PKC) known as InaC. These proteins interact with other proteins and have been shown to be necessary for shut off of the light response. In addition, proteins called arrestins bind metarhodopsin and prevent it from activating more Gq. A sodium-calcium exchanger known as CalX pumps the calcium out of the cell. It uses the inward sodium gradient to export calcium at a stoichiometry of 3 Na+/ 1 Ca++.[42]

TRP, InaC, and PLC form a signaling complex by binding a scaffolding protein called InaD. InaD contains five binding domains called PDZ domain proteins, which specifically bind the C termini of target proteins. Disruption of the complex by mutations in either the PDZ domains or the target proteins reduces the efficiency of signaling. For example, disruption of the interaction between InaC, the protein kinase C, and InaD results in a delay in inactivation of the light response.

Unlike vertebrate metarhodopsin, invertebrate metarhodopsin can be converted back into rhodopsin by absorbing a photon of orange light (580nm).

About two-thirds of the Drosophila brain is dedicated to visual processing.[43] Although the spatial resolution of their vision is significantly worse than that of humans, their temporal resolution is around 10 times better.

The wings of a fly are capable of beating up to 220 times per second.[citation needed] Flies fly via straight sequences of movement interspersed by rapid turns called saccades.[44] During these turns, a fly is able to rotate 90 in less than 50 milliseconds.[44]

Characteristics of Drosophila flight may be dominated by the viscosity of the air, rather than the inertia of the fly body, but the opposite case with inertia as the dominant force may occur.[44] However, subsequent work showed that while the viscous effects on the insect body during flight may be negligible, the aerodynamic forces on the wings themselves actually cause fruit flies' turns to be damped viscously.[45]

Drosophila is commonly considered a pest due to its tendency to infest habitations and establishments where fruit is found; the flies may collect in homes, restaurants, stores, and other locations.[3] Removal of an infestation can be difficult, as larvae may continue to hatch in nearby fruit even as the adult population is eliminated.

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Drosophila melanogaster - Wikipedia

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Ageing – Wikipedia

Wednesday, December 7th, 2016

Ageing, also spelled aging, is the process of becoming older. The term refers especially to human beings, many animals, and fungi, whereas for example bacteria, perennial plants and some simple animals are potentially immortal. In the broader sense, ageing can refer to single cells within an organism which have ceased dividing (cellular senescence) or to the population of a species (population ageing).

In humans, ageing represents the accumulation of changes in a human being over time,[1] encompassing physical, psychological, and social change. Reaction time, for example, may slow with age, while knowledge of world events and wisdom may expand. Ageing is among the greatest known risk factors for most human diseases:[2] of the roughly 150,000 people who die each day across the globe, about two thirds die from age-related causes.

The causes of ageing are unknown; current theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA breaks, oxidised DNA and/or mitochondrial malfunctions)[3] may cause biological systems to fail, or to the programmed ageing concept, whereby internal processes (such as DNA telomere shortening) may cause ageing. Programmed ageing should not be confused with programmed cell death (apoptosis).

The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats has motivated research into delaying and preventing ageing.

Human beings and members of other species, especially animals, necessarily experience ageing and mortality. Fungi, too, can age.[4] In contrast, many species can be considered immortal: for example, bacteria fission to produce daughter cells, strawberry plants grow runners to produce clones of themselves, and animals in the genus Hydra have a regenerative ability with which they avoid dying of old age.

Early life forms on Earth, starting at least 3.7 billion years ago,[5] were single-celled organisms. Such single-celled organisms (prokaryotes, protozoans, algae) multiply by fissioning into daughter cells, thus do not age and are innately immortal.[6][7]

Ageing and mortality of the individual organism became possible with the evolution of sexual reproduction,[8] which occurred with the emergence of the fungal/animal kingdoms approximately a billion years ago, and with the evolution of flowering plants 160 million years ago. The sexual organism could henceforth pass on some of its genetic material to produce new individuals and itself could become disposable with regards to the survival of its species.[8] This classic biological idea has however been perturbed recently by the discovery that the bacterium E. coli may split into distinguishable daughter cells, which opens the theoretical possibility of "age classes" among bacteria.[9]

Even within humans and other mortal species, there are cells with the potential for immortality: cancer cells which have lost the ability to die when maintained in cell culture such as the HeLa cell line,[10] and specific stem cells such as germ cells (producing ova and spermatozoa).[11] In artificial cloning, adult cells can be rejuvenated back to embryonic status and then used to grow a new tissue or animal without ageing.[12] Normal human cells however die after about 50 cell divisions in laboratory culture (the Hayflick Limit, discovered by Leonard Hayflick in 1961).[10]

A number of characteristic ageing symptoms are experienced by a majority or by a significant proportion of humans during their lifetimes.

Dementia becomes more common with age.[35] About 3% of people between the ages of 6574 have dementia, 19% between 75 and 84 and nearly half of those over 85 years of age.[36] The spectrum includes mild cognitive impairment and the neurodegenerative diseases of Alzheimer's disease, cerebrovascular disease, Parkinson's disease and Lou Gehrig's disease. Furthermore, many types of memory may decline with ageing, but not semantic memory or general knowledge such as vocabulary definitions, which typically increases or remains steady until late adulthood[37] (see Ageing brain). Intelligence may decline with age, though the rate may vary depending on the type and may in fact remain steady throughout most of the lifespan, dropping suddenly only as people near the end of their lives. Individual variations in rate of cognitive decline may therefore be explained in terms of people having different lengths of life.[38] There might be changes to the brain: after 20 years of age there may be a 10% reduction each decade in the total length of the brain's myelinated axons.[39][40]

Age can result in visual impairment, whereby non-verbal communication is reduced,[41] which can lead to isolation and possible depression. Macular degeneration causes vision loss and increases with age, affecting nearly 12% of those above the age of 80.[42] This degeneration is caused by systemic changes in the circulation of waste products and by growth of abnormal vessels around the retina.[43]

A distinction can be made between "proximal ageing" (age-based effects that come about because of factors in the recent past) and "distal ageing" (age-based differences that can be traced back to a cause early in person's life, such as childhood poliomyelitis).[38]

Ageing is among the greatest known risk factors for most human diseases.[2] Of the roughly 150,000 people who die each day across the globe, about two thirds100,000 per daydie from age-related causes. In industrialised nations, the proportion is higher, reaching 90%.[44][45][46]

At present, researchers are only just beginning to understand the biological basis of ageing even in relatively simple and short-lived organisms such as yeast.[47] Less still is known about mammalian ageing, in part due to the much longer lives in even small mammals such as the mouse (around 3 years). A primary model organism for studying ageing is the nematode C. elegans, thanks to its short lifespan of 23 weeks, the ability to easily perform genetic manipulations or suppress gene activity with RNA interference, and other factors.[48] Most known mutations and RNA interference targets that extend lifespan were first discovered in C. elegans.[49]

Factors that are proposed to influence biological ageing[50] fall into two main categories, programmed and damage-related. Programmed factors follow a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defence responses. Damage-related factors include internal and environmental assaults to living organisms that induce cumulative damage at various levels.[51]

There are three main metabolic pathways which can influence the rate of ageing:

It is likely that most of these pathways affect ageing separately, because targeting them simultaneously leads to additive increases in lifespan.[53]

The rate of ageing varies substantially across different species, and this, to a large extent, is genetically based. For example, numerous perennial plants ranging from strawberries and potatoes to willow trees typically produce clones of themselves by vegetative reproduction and are thus potentially immortal, while annual plants such as wheat and watermelons die each year and reproduce by sexual reproduction. In 2008 it was discovered that inactivation of only two genes in the annual plant Arabidopsis thaliana leads to its conversion into a potentially immortal perennial plant.[54]

Clonal immortality apart, there are certain species whose individual lifespans stand out among Earth's life-forms, including the bristlecone pine at 5062 years[55] (however Hayflick states that the bristlecone pine has no cells older than 30 years), invertebrates like the hard clam (known as quahog in New England) at 508 years,[56] the Greenland shark at 400 years,[57] fish like the sturgeon and the rockfish, and the sea anemone[58] and lobster.[59][60] Such organisms are sometimes said to exhibit negligible senescence.[61] The genetic aspect has also been demonstrated in studies of human centenarians.

In laboratory settings, researchers have demonstrated that selected alterations in specific genes can extend lifespan quite substantially in yeast and roundworms, less so in fruit flies and less again in mice. Some of the targeted genes have homologues across species and in some cases have been associated with human longevity.[62]

Caloric restriction substantially affects lifespan in many animals, including the ability to delay or prevent many age-related diseases.[103] Typically, this involves caloric intake of 6070% of what an ad libitum animal would consume, while still maintaining proper nutrient intake.[103] In rodents, this has been shown to increase lifespan by up to 50%;[104] similar effects occur for yeast and Drosophila.[103] No lifespan data exist for humans on a calorie-restricted diet,[76] but several reports support protection from age-related diseases.[105][106] Two major ongoing studies on rhesus monkeys initially revealed disparate results; while one study, by the University of Wisconsin, showed that caloric restriction does extend lifespan,[107] the second study, by the National Institute on Ageing (NIA), found no effects of caloric restriction on longevity.[108] Both studies nevertheless showed improvement in a number of health parameters. Notwithstanding the similarly low calorie intake, the diet composition differed between the two studies (notably a high sucrose content in the Wisconsin study), and the monkeys have different origins (India, China), initially suggesting that genetics and dietary composition, not merely a decrease in calories, are factors in longevity.[76] However, in a comparative analysis in 2014, the Wisconsin researchers found that the allegedly non-starved NIA control monkeys in fact are moderately underweight when compared with other monkey populations, and argued this was due to the NIA's apportioned feeding protocol in contrast to Wisconsin's truly unrestricted ad libitum feeding protocol.[109] They conclude that moderate calorie restriction rather than extreme calorie restriction is sufficient to produce the observed health and longevity benefits in the studied rhesus monkeys.[110]

In his book How and Why We Age, Hayflick says that caloric restriction may not be effective in humans, citing data from the Baltimore Longitudinal Study of Aging which shows that being thin does not favour longevity.[need quotation to verify][111] Similarly, it is sometimes claimed that moderate obesity in later life may improve survival, but newer research has identified confounding factors such as weight loss due to terminal disease. Once these factors are accounted for, the optimal body weight above age 65 corresponds to a leaner body mass index of 23 to 27.[112]

Alternatively, the benefits of dietary restriction can also be found by changing the macro nutrient profile to reduce protein intake without any changes to calorie level, resulting in similar increases in longevity.[113][114] Dietary protein restriction not only inhibits mTOR activity but also IGF-1, two mechanisms implicated in ageing.[74] Specifically, reducing leucine intake is sufficient to inhibit mTOR activity, achievable through reducing animal food consumption.[115][116]

The Mediterranean diet is credited with lowering the risk of heart disease and early death.[117][118] The major contributors to mortality risk reduction appear to be a higher consumption of vegetables, fish, fruits, nuts and monounsaturated fatty acids, i.e., olive oil.[119]

The amount of sleep has an impact on mortality. People who live the longest report sleeping for six to seven hours each night.[120][121] Lack of sleep (<5 hours) more than doubles the risk of death from cardiovascular disease, but too much sleep (>9 hours) is associated with a doubling of the risk of death, though not primarily from cardiovascular disease.[122] Sleeping more than 7 to 8 hours per day has been consistently associated with increased mortality, though the cause is probably other factors such as depression and socioeconomic status, which would correlate statistically.[123] Sleep monitoring of hunter-gatherer tribes from Africa and from South America has shown similar sleep patterns across continents: their average sleeping duration is 6.4 hours (with a summer/winter difference of 1 hour), afternoon naps (siestas) are uncommon, and insomnia is very rare (tenfold less than in industrial societies).[124]

Physical exercise may increase life expectancy.[125] People who participate in moderate to high levels of physical exercise have a lower mortality rate compared to individuals who are not physically active.[126] Moderate levels of exercise have been correlated with preventing aging and improving quality of life by reducing inflammatory potential.[127] The majority of the benefits from exercise are achieved with around 3500 metabolic equivalent (MET) minutes per week.[128] For example, climbing stairs 10 minutes, vacuuming 15 minutes, gardening 20 minutes, running 20 minutes, and walking or bicycling for 25 minutes on a daily basis would together achieve about 3000 MET minutes a week.[128]

Avoidance of chronic stress (as opposed to acute stress) is associated with a slower loss of telomeres in most but not all studies,[129][130] and with decreased cortisol levels. A chronically high cortisol level compromises the immune system, causes cardiac damage/arterosclerosis and is associated with facial ageing, and the latter in turn is a marker for increased morbidity and mortality.[131][132] Stress can be countered by social connection, spirituality, and (for men more clearly than for women) married life, all of which are associated with longevity.[133][134][135]

The following drugs and interventions have been shown to retard or reverse the biological effects of ageing in animal models, but none has yet been proven to do so in humans.

Evidence in both animals and humans suggests that resveratrol may be a caloric restriction mimetic.[136]

As of 2015 metformin was under study for its potential effect on slowing ageing in the worm C.elegans and the cricket.[137] Its effect on otherwise healthy humans is unknown.[137]

Rapamycin was first shown to extend lifespan in eukaryotes in 2006 by Powers et al. who showed a dose-responsive effect of rapamycin on lifespan extension in yeast cells.[138] In a 2009 study, the lifespans of mice fed rapamycin were increased between 28 and 38% from the beginning of treatment, or 9 to 14% in total increased maximum lifespan. Of particular note, the treatment began in mice aged 20 months, the equivalent of 60 human years.[139] Rapamycin has subsequently been shown to extend mouse lifespan in several separate experiments,[140][141] and is now being tested for this purpose in nonhuman primates (the marmoset monkey).[142]

Cancer geneticist Ronald A. DePinho and his colleagues published research in mice where telomerase activity was first genetically removed. Then, after the mice had prematurely aged, they restored telomerase activity by reactivating the telomerase gene. As a result, the mice were rejuvenated: Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver, intestines and brain, recuperated from their degenerated state. "[The finding] offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working" says Ronald DePinho. However, activating telomerase in humans could potentially encourage the growth of tumours.[143]

Most known genetic interventions in C. elegans increase lifespan by 1.5 to 2.5-fold. As of 2009[update], the record for lifespan extension in C. elegans is a single-gene mutation which increases adult survival by tenfold.[49] The strong conservation of some of the mechanisms of ageing discovered in model organisms imply that they may be useful in the enhancement of human survival. However, the benefits may not be proportional; longevity gains are typically greater in C. elegans than fruit flies, and greater in fruit flies than in mammals. One explanation for this is that mammals, being much longer-lived, already have many traits which promote lifespan.[49]

Some research effort is directed to slow ageing and extend healthy lifespan.[144][145][146]

The US National Institute on Aging currently funds an intervention testing programme, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice.[147] Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals and lax mouse husbandry conditions.[citation needed] The intervention testing programme aims to address this by conducting parallel experiments at three internationally recognised mouse ageing-centres, the Barshop Institute at UTHSCSA, the University of Michigan at Ann Arbor and the Jackson Laboratory.

Several companies and organisations, such as Google Calico, Human Longevity, Craig Venter, Gero,[148]SENS Research Foundation, and Science for Life Extension in Russia,[149] declared stopping or delaying ageing as their goal.

Prizes for extending lifespan and slowing ageing in mammals exist. The Methuselah Foundation offers the Mprize. Recently, the $1 Million Palo Alto Longevity Prize was launched. It is a research incentive prize to encourage teams from all over the world to compete in an all-out effort to "hack the code" that regulates our health and lifespan. It was founded by Joon Yun.[150][151][152][153][154]

Different cultures express age in different ways. The age of an adult human is commonly measured in whole years since the day of birth. Arbitrary divisions set to mark periods of life may include: juvenile (via infancy, childhood, preadolescence, adolescence), early adulthood, middle adulthood, and late adulthood. More casual terms may include "teenagers," "tweens," "twentysomething", "thirtysomething", etc. as well as "vicenarian", "tricenarian", "quadragenarian", etc.

Most legal systems define a specific age for when an individual is allowed or obliged to do particular activities. These age specifications include voting age, drinking age, age of consent, age of majority, age of criminal responsibility, marriageable age, age of candidacy, and mandatory retirement age. Admission to a movie for instance, may depend on age according to a motion picture rating system. A bus fare might be discounted for the young or old. Each nation, government and non-governmental organisation has different ways of classifying age. In other words, chronological ageing may be distinguished from "social ageing" (cultural age-expectations of how people should act as they grow older) and "biological ageing" (an organism's physical state as it ages).[155]

In a UNFPA report about ageing in the 21st century, it highlighted the need to "Develop a new rights-based culture of ageing and a change of mindset and societal attitudes towards ageing and older persons, from welfare recipients to active, contributing members of society."[156] UNFPA said that this "requires, among others, working towards the development of international human rights instruments and their translation into national laws and regulations and affirmative measures that challenge age discrimination and recognise older people as autonomous subjects."[156] Older persons make contributions to society including caregiving and volunteering. For example, "A study of Bolivian migrants who [had] moved to Spain found that 69% left their children at home, usually with grandparents. In rural China, grandparents care for 38% of children aged under five whose parents have gone to work in cities."[156]

Population ageing is the increase in the number and proportion of older people in society. Population ageing has three possible causes: migration, longer life expectancy (decreased death rate) and decreased birth rate. Ageing has a significant impact on society. Young people tend to have fewer legal privileges (if they are below the age of majority), they are more likely to push for political and social change, to develop and adopt new technologies, and to need education. Older people have different requirements from society and government, and frequently have differing values as well, such as for property and pension rights.[157]

In the 21st century, one of the most significant population trends is ageing.[158] Currently, over 11% of the world's current population are people aged 60 and older and the United Nations Population Fund (UNFPA) estimates that by 2050 that number will rise to approximately 22%.[156] Ageing has occurred due to development which has enabled better nutrition, sanitation, health care, education and economic well-being. Consequently, fertility rates have continued to decline and life expectancy have risen. Life expectancy at birth is over 80 now in 33 countries. Ageing is a "global phenomenon," that is occurring fastest in developing countries, including those with large youth populations, and poses social and economic challenges to the work which can be overcome with "the right set of policies to equip individuals, families and societies to address these challenges and to reap its benefits."[159]

As life expectancy rises and birth rates decline in developed countries, the median age rises accordingly. According to the United Nations, this process is taking place in nearly every country in the world.[160] A rising median age can have significant social and economic implications, as the workforce gets progressively older and the number of old workers and retirees grows relative to the number of young workers. Older people generally incur more health-related costs than do younger people in the workplace and can also cost more in worker's compensation and pension liabilities.[161] In most developed countries an older workforce is somewhat inevitable. In the United States for instance, the Bureau of Labor Statistics estimates that one in four American workers will be 55 or older by 2020.[161]

Among the most urgent concerns of older persons worldwide is income security. This poses challenges for governments with ageing populations to ensure investments in pension systems continues in order to provide economic independence and reduce poverty in old age. These challenges vary for developing and developed countries. UNFPA stated that, "Sustainability of these systems is of particular concern, particularly in developed countries, while social protection and old-age pension coverage remain a challenge for developing countries, where a large proportion of the labour force is found in the informal sector."[156]

The global economic crisis has increased financial pressure to ensure economic security and access to health care in old age. In order to elevate this pressure "social protection floors must be implemented in order to guarantee income security and access to essential health and social services for all older persons and provide a safety net that contributes to the postponement of disability and prevention of impoverishment in old age."[156]

It has been argued that population ageing has undermined economic development.[162] Evidence suggests that pensions, while making a difference to the well-being of older persons, also benefit entire families especially in times of crisis when there may be a shortage or loss of employment within households. A study by the Australian Government in 2003 estimated that "women between the ages of 65 and 74 years contribute A$16 billion per year in unpaid caregiving and voluntary work. Similarly, men in the same age group contributed A$10 billion per year."[156]

Due to increasing share of the elderly in the population, health care expenditures will continue to grow relative to the economy in coming decades. This has been considered as a negative phenomenon and effective strategies like labour productivity enhancement should be considered to deal with negative consequences of ageing.[163]

In the field of sociology and mental health, ageing is seen in five different views: ageing as maturity, ageing as decline, ageing as a life-cycle event, ageing as generation, and ageing as survival.[164] Positive correlates with ageing often include economics, employment, marriage, children, education, and sense of control, as well as many others. The social science of ageing includes disengagement theory, activity theory, selectivity theory, and continuity theory. Retirement, a common transition faced by the elderly, may have both positive and negative consequences.[165] As cyborgs currently are on the rise some theorists argue there is a need to develop new definitions of ageing and for instance a bio-techno-social definition of ageing has been suggested.[166]

With age inevitable biological changes occur that increase the risk of illness and disability. UNFPA states that,[159]

"A life-cycle approach to health care one that starts early, continues through the reproductive years and lasts into old age is essential for the physical and emotional well-being of older persons, and, indeed, all people. Public policies and programmes should additionally address the needs of older impoverished people who cannot afford health care."

Many societies in Western Europe and Japan have ageing populations. While the effects on society are complex, there is a concern about the impact on health care demand. The large number of suggestions in the literature for specific interventions to cope with the expected increase in demand for long-term care in ageing societies can be organised under four headings: improve system performance; redesign service delivery; support informal caregivers; and shift demographic parameters.[167]

However, the annual growth in national health spending is not mainly due to increasing demand from ageing populations, but rather has been driven by rising incomes, costly new medical technology, a shortage of health care workers and informational asymmetries between providers and patients.[168] A number of health problems become more prevalent as people get older. These include mental health problems as well as physical health problems, especially dementia.

It has been estimated that population ageing only explains 0.2 percentage points of the annual growth rate in medical spending of 4.3% since 1970. In addition, certain reforms to the Medicare system in the United States decreased elderly spending on home health care by 12.5% per year between 1996 and 2000.[169]

Positive self-perception of health has been correlated with higher well-being and reduced mortality in the elderly.[170][171] Various reasons have been proposed for this association; people who are objectively healthy may naturally rate their health better than that of their ill counterparts, though this link has been observed even in studies which have controlled for socioeconomic status, psychological functioning and health status.[172] This finding is generally stronger for men than women,[171] though this relationship is not universal across all studies and may only be true in some circumstances.[172]

As people age, subjective health remains relatively stable, even though objective health worsens.[173] In fact, perceived health improves with age when objective health is controlled in the equation.[174] This phenomenon is known as the "paradox of ageing." This may be a result of social comparison;[175] for instance, the older people get, the more they may consider themselves in better health than their same-aged peers.[176] Elderly people often associate their functional and physical decline with the normal ageing process.[177][178]

The concept of successful ageing can be traced back to the 1950s and was popularised in the 1980s. Traditional definitions of successful ageing have emphasised absence of physical and cognitive disabilities.[179] In their 1987 article, Rowe and Kahn characterised successful ageing as involving three components: a) freedom from disease and disability, b) high cognitive and physical functioning, and c) social and productive engagement.[180]

The ancient Greek dramatist Euripides (5th century BC) describes the multiply-headed mythological monster Hydra as having a regenerative capacity which makes it immortal, which is the historical background to the name of the biological genus Hydra. The Book of Job (c. 6th century BC) describes human lifespan as inherently limited and makes a comparison with the innate immortality that a felled tree may have when undergoing vegetative regeneration.[181]

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Ashkenazi Jews – Wikipedia

Wednesday, December 7th, 2016

Ashkenazi Jews ( Y'hudey Ashkenaz in Ashkenazi Hebrew) Total population (10[1]11.2[2] million) Regions with significant populations United States 56 million[3] Israel 2.8 million[1][4] Russia 194,000500,000 Argentina 300,000 United Kingdom 260,000 Canada 240,000 France 200,000 Germany 200,000 Ukraine 150,000 Australia 120,000 South Africa 80,000 Belarus 80,000 Hungary 75,000 Chile 70,000 Belgium 30,000 Brazil 30,000 Netherlands 30,000 Moldova 30,000 Poland 25,000 Mexico 18,500 Sweden 18,000 Latvia 10,000 Romania 10,000 Austria 9,000 New Zealand 5,000 Azerbaijan 4,300 Lithuania 4,000 Czech Republic 3,000 Slovakia 3,000 Estonia 1,000 Languages Historical: Yiddish Modern: Local languages, primarily:English, Hebrew, Russian Religion Judaism, some secular, irreligious Related ethnic groups Sephardi Jews, Mizrahi Jews, Samaritans,[5][5][6][7]Kurds,[7] other Levantines (Druze, Assyrians,[5][6]Arabs[5][6][8][9]), Mediterranean groups[10][11][12][13][14]

Ashkenazi Jews, also known as Ashkenazic Jews or simply Ashkenazim (Hebrew: , Ashkenazi Hebrew pronunciation: [aknazim], singular: [aknazi], Modern Hebrew: [akenazim, akenazi]; also Y'hudey Ashkenaz),[15] are a Jewish diaspora population who coalesced as a distinct community in the Holy Roman Empire around the end of the first millennium.[16] The traditional diaspora language of Ashkenazi Jews is Yiddish (which incorporates several dialects), while until recently Hebrew was only used as a sacred language.

The Ashkenazim settled and established communities throughout Central and Eastern Europe, which was their primary region of concentration and residence from the Middle Ages until recent times. They subsequently evolved their own distinctive culture and diasporic identities.[17] Throughout their time in Europe, the Ashkenazim have made many important contributions to philosophy, scholarship, literature, art, music and science.[18][19][20][21]

In the late Middle Ages, the center of gravity of the Ashkenazi population shifted steadily eastward,[22] moving out of the Holy Roman Empire into the Pale of Settlement (comprising parts of present-day Belarus, Latvia, Lithuania, Moldova, Poland, Russia, and Ukraine).[23][24] In the course of the late 18th and 19th centuries, those Jews who remained in or returned to the German lands experienced a cultural reorientation; under the influence of the Haskalah and the struggle for emancipation, as well the intellectual and cultural ferment in urban centers, they gradually abandoned the use of Yiddish, while developing new forms of Jewish religious life and cultural identity.[25]

The genocidal impact of the Holocaust (the mass murder of approximately six million Jews during World War II) devastated the Ashkenazim and their culture, affecting almost every Jewish family.[26][27] It is estimated that in the 11th century Ashkenazi Jews composed only three percent of the world's Jewish population, while at their peak in 1931 they accounted for 92 percent of the world's Jews. Immediately prior to the Holocaust, the number of Jews in the world stood at approximately 16.7 million.[28] Statistical figures vary for the contemporary demography of Ashkenazi Jews, oscillating between 10 million[1] and 11.2 million.[2]Sergio DellaPergola in a rough calculation of Sephardic and Mizrahi Jews, implies that Ashkenazi make up less than 74% of Jews worldwide.[29] Other estimates place Ashkenazi Jews as making up about 75% of Jews worldwide.[30]

Genetic studies on Ashkenazimresearching both their paternal and maternal lineagessuggest a significant proportion of West Asian ancestry. Those studies have arrived at diverging conclusions regarding both the degree and the sources of their European ancestry, and have generally focused on the extent of the European genetic origin observed in Ashkenazi maternal lineages.[31] Ashkenazi Jews are popularly contrasted with Sephardi Jews (also called Sephardim), who are descendants of Jews from the Iberian Peninsula (though there are other groups as well). There are some differences in how the two groups pronounce certain Hebrew letters and in points of ritual.

The name Ashkenazi derives from the biblical figure of Ashkenaz, the first son of Gomer, son of Khaphet, son of Noah, and a Japhetic patriarch in the Table of Nations (Genesis 10). The name of Gomer has often been linked to the ethnonym Cimmerians. Biblical Ashkenaz is usually derived from Assyrian Akza (cuneiform Akuzai/Ikuzai), a people who expelled the Cimmerians from the Armenian area of the Upper Euphrates,[32] whose name is usually associated with the name of the Scythians.[33][34] The intrusive n in the Biblical name is likely due to a scribal error confusing a waw with a nun .[34][35][36]

In Jeremiah 51:27, Ashkenaz figures as one of three kingdoms in the far north, the others being Minni and Ararat, perhaps corresponding to Urartu, called on by God to resist Babylon.[36][37]

In the Yoma tractate of the Babylonian Talmud the name Gomer is rendered as Germania, which elsewhere in rabbinical literature was identified with Germanikia in northwestern Syria, but later became associated with Germania. Ashkenaz is linked to Scandza/Scanzia, viewed as the cradle of Germanic tribes, as early as a 6th-century gloss to the Historia Ecclesiastica of Eusebius.[38] In the 10th-century History of Armenia of Yovhannes Drasxanakertc'i (1.15) Ashkenaz was associated with Armenia,[39] as it was occasionally in Jewish usage, where its denotation extended at times to Adiabene, Khazaria, Crimea and areas to the east.[40] His contemporary Saadia Gaon identified Ashkenaz with the Saquliba or Slavic territories,[41] and such usage covered also the lands of tribes neighboring the Slavs, and Eastern and Central Europe.[40] In modern times, Samuel Krauss identified the Biblical "Ashkenaz" with Khazaria.[42]

Sometime in the early medieval period, the Jews of central and eastern Europe came to be called by this term.[36] In conformity with the custom of designating areas of Jewish settlement with biblical names, Spain was denominated Sefarad (Obadiah 20), France was called Tsarefat (1 Kings 17:9), and Bohemia was called the Land of Canaan.[43] By the high medieval period, Talmudic commentators like Rashi began to use Ashkenaz/Eretz Ashkenaz to designate Germany, earlier known as Loter,[36][38] where, especially in the Rhineland communities of Speyer, Worms and Mainz, the most important Jewish communities arose.[44] Rashi uses leshon Ashkenaz (Ashkenazi language) to describe German speech, and Byzantium and Syrian Jewish letters referred to the Crusaders as Ashkenazim.[38] Given the close links between the Jewish communities of France and Germany following the Carolingian unification, the term Ashkenazi came to refer to both the Jews of medieval Germany and France.[45]

Outside of their origins in ancient Israel, the history of Ashkenazim is shrouded in mystery,[46] and many theories have arisen speculating on their emergence as a distinct community of Jews.[47] The most well supported theory is the one that details a Jewish migration from Israel through what is now Italy and other parts of southern Europe.[48] The historical record attests to Jewish communities in southern Europe since pre-Christian times.[49] Many Jews were denied full Roman citizenship until 212 CE, when Emperor Caracalla granted all free peoples this privilege. Jews were required to pay a poll tax until the reign of Emperor Julian in 363. In the late Roman Empire, Jews were free to form networks of cultural and religious ties and enter into various local occupations. But, after Christianity became the official religion of Rome and Constantinople in 380, Jews were increasingly marginalized.

The history of Jews in Greece goes back to at least the Archaic Era of Greece, when the classical culture of Greece was undergoing a process of formalization after the Greek Dark Age. The Greek historian Herodotus knew of the Jews, whom he called "Palestinian Syrians",[citation needed] and listed them among the levied naval forces in service of the invading Persians. While Jewish monotheism was not deeply affected by Greek Polytheism, the Greek way of living was attractive for many wealthier Jews.[50] The Synagogue in the Agora of Athens is dated to the period between 267 and 396 CE. The Stobi Synagogue in Macedonia, was built on the ruins of a more ancient synagogue in the 4th century, while later in the 5th century, the synagogue was transformed into Christian basilica.[51]Hellenistic Judaism thrived in Antioch and Alexandria, many of these Greek-speaking Jews would convert to Christianity.[52] Sporadic[53]epigraphic evidence in grave site excavations, particularly in Brigetio (Szny), Aquincum (buda), Intercisa (Dunajvros), Triccinae (Srvr), Savaria (Szombathely), Sopianae (Pcs) in Hungary, and Osijek in Croatia, attest to the presence of Jews after the 2nd and 3rd centuries where Roman garrisons were established,[54] There was a sufficient number of Jews in Pannonia to form communities and build a synagogue. Jewish troops were among the Syrian soldiers transferred there, and replenished from the Middle East, after 175 C.E. Jews and especially Syrians came from Antioch, Tarsus and Cappadocia. Others came from Italy and the Hellenized parts of the Roman empire. The excavations suggest they first lived in isolated enclaves attached to Roman legion camps, and intermarried among other similar oriental families within the military orders of the region.[53]Raphael Patai states that later Roman writers remarked that they differed little in either customs, manner of writing, or names from the people among whom they dwelt; and it was especially difficult to differentiate Jews from the Syrians.[55][56] After Pannonia was ceded to the Huns in 433, the garrison populations were withdrawn to Italy, and only a few, enigmatic traces remain of a possible Jewish presence in the area some centuries later.[57]

No evidence has yet been found of a Jewish presence in antiquity in Germany beyond its Roman border, nor in Eastern Europe. In Gaul and Germany itself, with the possible exception of Trier and Cologne, the archeological evidence suggests at most a fleeting presence of very few Jews, primarily itinerant traders or artisans.[58] A substantial Jewish population emerged in northern Gaul by the Middle Ages,[59] but Jewish communities existed in 465 CE in Brittany, in 524 CE in Valence, and in 533 CE in Orleans.[60] Throughout this period and into the early Middle Ages, some Jews assimilated into the dominant Greek and Latin cultures, mostly through conversion to Christianity.[61][bettersourceneeded] King Dagobert I of the Franks expelled the Jews from his Merovingian kingdom in 629. Jews in former Roman territories faced new challenges as harsher anti-Jewish Church rulings were enforced.

Charlemagne's expansion of the Frankish empire around 800, including northern Italy and Rome, brought on a brief period of stability and unity in Francia. This created opportunities for Jewish merchants to settle again north of the Alps. Charlemagne granted the Jews freedoms similar to those once enjoyed under the Roman Empire. In addition, Jews from southern Italy, fleeing religious persecution, began to move into central Europe.[citation needed] Returning to Frankish lands, many Jewish merchants took up occupations in finance and commerce, including money lending, or usury. (Church legislation banned Christians from lending money in exchange for interest.) From Charlemagne's time to the present, Jewish life in northern Europe is well documented. By the 11th century, when Rashi of Troyes wrote his commentaries, Jews in what came to be known as "Ashkenaz" were known for their halakhic learning, and Talmudic studies. They were criticized by Sephardim and other Jewish scholars in Islamic lands for their lack of expertise in Jewish jurisprudence (dinim) and general ignorance of Hebrew linguistics and literature.[62]Yiddish emerged as a result of Judeo-Latin language contact with various High German vernaculars in the medieval period.[63] It is a Germanic language written with Hebrew letters, and heavily influenced by Hebrew and Aramaic, with some elements of Romance and later Slavic languages.[64]

Historical records show evidence of Jewish communities north of the Alps and Pyrenees as early as the 8th and 9th century. By the 11th century Jewish settlers, moving from southern European and Middle Eastern centers, appear to have begun to settle in the north, especially along the Rhine, often in response to new economic opportunities and at the invitation of local Christian rulers. Thus Baldwin V, Count of Flanders, invited Jacob ben Yekutiel and his fellow Jews to settle in his lands; and soon after the Norman Conquest of England, William the Conqueror likewise extended a welcome to continental Jews to take up residence there. Bishop Rdiger Huzmann called on the Jews of Mainz to relocate to Speyer. In all of these decisions, the idea that Jews had the know-how and capacity to jump-start the economy, improve revenues, and enlarge trade seems to have played a prominent role.[65] Typically Jews relocated close to the markets and churches in town centres, where, though they came under the authority of both royal and ecclesiastical powers, they were accorded administrative autonomy.[65]

In the 11th century, both Rabbinic Judaism and the culture of the Babylonian Talmud that underlies it became established in southern Italy and then spread north to Ashkenaz.[66]

The Jewish communities along the Rhine river from Cologne to Mainz were decimated in the Rhineland massacres of 1096. With the onset of the Crusades in 1095, and the expulsions from England (1290), France (1394), and parts of Germany (15th century), Jewish migration pushed eastward into Poland (10th century), Lithuania (10th century), and Russia (12th century). Over this period of several hundred years, some have suggested, Jewish economic activity was focused on trade, business management, and financial services, due to several presumed factors: Christian European prohibitions restricting certain activities by Jews, preventing certain financial activities (such as "usurious" loans)[67] between Christians, high rates of literacy, near universal male education, and ability of merchants to rely upon and trust family members living in different regions and countries.

By the 15th century, the Ashkenazi Jewish communities in Poland were the largest Jewish communities of the Diaspora.[68] This area, which eventually fell under the domination of Russia, Austria, and Prussia (Germany), would remain the main center of Ashkenazi Jewry until the Holocaust.

The answer to why there was so little assimilation of Jews in central and eastern Europe for so long would seem to lie in part in the probability that the alien surroundings in central and eastern Europe were not conducive, though contempt did not prevent some assimilation. Furthermore, Jews lived almost exclusively in shtetls, maintained a strong system of education for males, heeded rabbinic leadership, and scorned the life-style of their neighbors; and all of these tendencies increased with every outbreak of antisemitism.[69]

In the first half of the 11th century, Hai Gaon refers to questions that had been addressed to him from Ashkenaz, by which he undoubtedly means Germany. Rashi in the latter half of the 11th century refers to both the language of Ashkenaz[70] and the country of Ashkenaz.[71] During the 12th century, the word appears quite frequently. In the Mahzor Vitry, the kingdom of Ashkenaz is referred to chiefly in regard to the ritual of the synagogue there, but occasionally also with regard to certain other observances.[72]

In the literature of the 13th century, references to the land and the language of Ashkenaz often occur. Examples include Solomon ben Aderet's Responsa (vol. i., No. 395); the Responsa of Asher ben Jehiel (pp.4, 6); his Halakot (Berakot i. 12, ed. Wilna, p.10); the work of his son Jacob ben Asher, Tur Orach Chayim (chapter 59); the Responsa of Isaac ben Sheshet (numbers 193, 268, 270).

In the Midrash compilation, Genesis Rabbah, Rabbi Berechiah mentions Ashkenaz, Riphath, and Togarmah as German tribes or as German lands. It may correspond to a Greek word that may have existed in the Greek dialect of the Jews in Syria Palaestina, or the text is corrupted from "Germanica." This view of Berechiah is based on the Talmud (Yoma 10a; Jerusalem Talmud Megillah 71b), where Gomer, the father of Ashkenaz, is translated by Germamia, which evidently stands for Germany, and which was suggested by the similarity of the sound.

In later times, the word Ashkenaz is used to designate southern and western Germany, the ritual of which sections differs somewhat from that of eastern Germany and Poland. Thus the prayer-book of Isaiah Horowitz, and many others, give the piyyutim according to the Minhag of Ashkenaz and Poland.

According to 16th-century mystic Rabbi Elijah of Chelm, Ashkenazi Jews lived in Jerusalem during the 11th century. The story is told that a German-speaking Jew saved the life of a young German man surnamed Dolberger. So when the knights of the First Crusade came to siege Jerusalem, one of Dolberger's family members who was among them rescued Jews in Palestine and carried them back to Worms to repay the favor.[73] Further evidence of German communities in the holy city comes in the form of halakhic questions sent from Germany to Jerusalem during the second half of the 11th century.[74]

Material relating to the history of German Jews has been preserved in the communal accounts of certain communities on the Rhine, a Memorbuch, and a Liebesbrief, documents that are now part of the Sassoon Collection.[75]Heinrich Graetz has also added to the history of German Jewry in modern times in the abstract of his seminal work, History of the Jews, which he entitled "Volksthmliche Geschichte der Juden."

In an essay on Sephardi Jewry, Daniel Elazar at the Jerusalem Center for Public Affairs[76] summarized the demographic history of Ashkenazi Jews in the last thousand years, noting that at the end of the 11th century, 97% of world Jewry was Sephardic and 3% Ashkenazi; by the end of XVI century, the: 'Treaty on the redemption of captives', by Gracian of the God's Mother, Mercy Priest, who was imprisoned by Turks, cites a Tunisian Hebrew, made captive when arriving to Gaeta, who aided others with money, named: 'Simon Escanasi', in the mid-17th century, "Sephardim still outnumbered Ashkenazim three to two", but by the end of the 18th century, "Ashkenazim outnumbered Sephardim three to two, the result of improved living conditions in Christian Europe versus the Ottoman Muslim world."[76] By 1931, Ashkenazi Jews accounted for nearly 92% of world Jewry.[76] These factors are sheer demography showing the migration patterns of Jews from Southern and Western Europe to Central and Eastern Europe.

In 1740 a family from Lithuania became the first Ashkenazi Jews to settle in the Jewish Quarter of Jerusalem.[77]

In the generations after emigration from the west, Jewish communities in places like Poland, Russia, and Belarus enjoyed a comparatively stable socio-political environment. A thriving publishing industry and the printing of hundreds of biblical commentaries precipitated the development of the Hasidic movement as well as major Jewish academic centers.[78] After two centuries of comparative tolerance in the new nations, massive westward emigration occurred in the 19th and 20th centuries in response to pogroms in the east and the economic opportunities offered in other parts of the world. Ashkenazi Jews have made up the majority of the American Jewish community since 1750.[68]

In the context of the European Enlightenment, Jewish emancipation began in 18th century France and spread throughout Western and Central Europe. Disabilities that had limited the rights of Jews since the Middle Ages were abolished, including the requirements to wear distinctive clothing, pay special taxes, and live in ghettos isolated from non-Jewish communities, and the prohibitions on certain professions. Laws were passed to integrate Jews into their host countries, forcing Ashkenazi Jews to adopt family names (they had formerly used patronymics). Newfound inclusion into public life led to cultural growth in the Haskalah, or Jewish Enlightenment, with its goal of integrating modern European values into Jewish life.[79] As a reaction to increasing antisemitism and assimilation following the emancipation, Zionism was developed in central Europe.[80] Other Jews, particularly those in the Pale of Settlement, turned to socialism. These tendencies would be united in Labor Zionism, the founding ideology of the State of Israel.

Of the estimated 8.8 million Jews living in Europe at the beginning of World War II, the majority of whom were Ashkenazi, about 6 million more than two-thirds were systematically murdered in the Holocaust. These included 3 million of 3.3 million Polish Jews (91%); 900,000 of 1.5 million in Ukraine (60%); and 5090% of the Jews of other Slavic nations, Germany, Hungary, and the Baltic states, and over 25% of the Jews in France. Sephardi communities suffered similar depletions in a few countries, including Greece, the Netherlands and the former Yugoslavia.[81] As the large majority of the victims were Ashkenazi Jews, their percentage dropped from nearly 92% of world Jewry in 1931 to nearly 80% of world Jewry today.[76] The Holocaust also effectively put an end to the dynamic development of the Yiddish language in the previous decades, as the vast majority of the Jewish victims of the Holocaust, around 5 million, were Yiddish speakers.[82] Many of the surviving Ashkenazi Jews emigrated to countries such as Israel, Canada, Argentina, Australia, and the United States after the war.

Following the Holocaust, some sources place Ashkenazim today as making up approximately 8385 percent of Jews worldwide,[83][84][85][86] while Sergio DellaPergola in a rough calculation of Sephardic and Mizrahi Jews, implies that Ashkenazi make up a notably lower figure, less than 74%.[29] Other estimates place Ashkenazi Jews as making up about 75% of Jews worldwide.[30] Ashkenazi Jews constitute around 3536% of Israel's total population, or 47.5% of Israel's Jewish population.[87][88]

In Israel, the term Ashkenazi is now used in a manner unrelated to its original meaning, often applied to all Jews who settled in Europe and sometimes including those whose ethnic background is actually Sephardic. Jews of any non-Ashkenazi background, including Mizrahi, Yemenite, Kurdish and others who have no connection with the Iberian Peninsula, have similarly come to be lumped together as Sephardic. Jews of mixed background are increasingly common, partly because of intermarriage between Ashkenazi and non-Ashkenazi, and partly because many do not see such historic markers as relevant to their life experiences as Jews.[89]

Religious Ashkenazi Jews living in Israel are obliged to follow the authority of the chief Ashkenazi rabbi in halakhic matters. In this respect, a religiously Ashkenazi Jew is an Israeli who is more likely to support certain religious interests in Israel, including certain political parties. These political parties result from the fact that a portion of the Israeli electorate votes for Jewish religious parties; although the electoral map changes from one election to another, there are generally several small parties associated with the interests of religious Ashkenazi Jews. The role of religious parties, including small religious parties that play important roles as coalition members, results in turn from Israel's composition as a complex society in which competing social, economic, and religious interests stand for election to the Knesset, a unicameral legislature with 120 seats.[90]

People of Ashkenazi descent constitute around 47.5% of Israeli Jews (and therefore 3536% of Israelis).[4] They have played a prominent role in the economy, media, and politics[91] of Israel since its founding. During the first decades of Israel as a state, strong cultural conflict occurred between Sephardic and Ashkenazi Jews (mainly east European Ashkenazim). The roots of this conflict, which still exists to a much smaller extent in present-day Israeli society, are chiefly attributed to the concept of the "melting pot".[92] That is to say, all Jewish immigrants who arrived in Israel were strongly encouraged to "melt down" their own particular exilic identities within the general social "pot" in order to become Israeli.[93]

The Ashkenazi Chief Rabbis in the Yishuv and Israel include:

Religious Jews have Minhagim, customs, in addition to Halakha, or religious law, and different interpretations of law. Different groups of religious Jews in different geographic areas historically adopted different customs and interpretations. On certain issues, Orthodox Jews are required to follow the customs of their ancestors, and do not believe they have the option of picking and choosing. For this reason, observant Jews at times find it important for religious reasons to ascertain who their household's religious ancestors are in order to know what customs their household should follow. These times include, for example, when two Jews of different ethnic background marry, when a non-Jew converts to Judaism and determines what customs to follow for the first time, or when a lapsed or less observant Jew returns to traditional Judaism and must determine what was done in his or her family's past. In this sense, "Ashkenazic" refers both to a family ancestry and to a body of customs binding on Jews of that ancestry. Reform Judaism, which does not necessarily follow those minhagim, did nonetheless originate among Ashkenazi Jews.[94]

In a religious sense, an Ashkenazi Jew is any Jew whose family tradition and ritual follows Ashkenazi practice. Until the Ashkenazi community first began to develop in the Early Middle Ages, the centers of Jewish religious authority were in the Islamic world, at Baghdad and in Islamic Spain. Ashkenaz (Germany) was so distant geographically that it developed a minhag of its own. Ashkenazi Hebrew came to be pronounced in ways distinct from other forms of Hebrew.[95]

In this respect, the counterpart of Ashkenazi is Sephardic, since most non-Ashkenazi Orthodox Jews follow Sephardic rabbinical authorities, whether or not they are ethnically Sephardic. By tradition, a Sephardic or Mizrahi woman who marries into an Orthodox or Haredi Ashkenazi Jewish family raises her children to be Ashkenazi Jews; conversely an Ashkenazi woman who marries a Sephardi or Mizrahi man is expected to take on Sephardic practice and the children inherit a Sephardic identity, though in practice many families compromise. A convert generally follows the practice of the beth din that converted him or her. With the integration of Jews from around the world in Israel, North America, and other places, the religious definition of an Ashkenazi Jew is blurring, especially outside Orthodox Judaism.[96]

New developments in Judaism often transcend differences in religious practice between Ashkenazi and Sephardic Jews. In North American cities, social trends such as the chavurah movement, and the emergence of "post-denominational Judaism"[97][98] often bring together younger Jews of diverse ethnic backgrounds. In recent years, there has been increased interest in Kabbalah, which many Ashkenazi Jews study outside of the Yeshiva framework. Another trend is the new popularity of ecstatic worship in the Jewish Renewal movement and the Carlebach style minyan, both of which are nominally of Ashkenazi origin.[99]

Culturally, an Ashkenazi Jew can be identified by the concept of Yiddishkeit, which means "Jewishness" in the Yiddish language.[100]Yiddishkeit is specifically the Jewishness of Ashkenazi Jews.[101] Before the Haskalah and the emancipation of Jews in Europe, this meant the study of Torah and Talmud for men, and a family and communal life governed by the observance of Jewish Law for men and women. From the Rhineland to Riga to Romania, most Jews prayed in liturgical Ashkenazi Hebrew, and spoke Yiddish in their secular lives. But with modernization, Yiddishkeit now encompasses not just Orthodoxy and Hasidism, but a broad range of movements, ideologies, practices, and traditions in which Ashkenazi Jews have participated and somehow retained a sense of Jewishness. Although a far smaller number of Jews still speak Yiddish, Yiddishkeit can be identified in manners of speech, in styles of humor, in patterns of association. Broadly speaking, a Jew is one who associates culturally with Jews, supports Jewish institutions, reads Jewish books and periodicals, attends Jewish movies and theater, travels to Israel, visits historical synagogues, and so forth. It is a definition that applies to Jewish culture in general, and to Ashkenazi Yiddishkeit in particular.

As Ashkenazi Jews moved away from Europe, mostly in the form of aliyah to Israel, or immigration to North America, and other English-speaking areas such as South Africa; and Europe (particularly France) and Latin America, the geographic isolation that gave rise to Ashkenazim has given way to mixing with other cultures, and with non-Ashkenazi Jews who, similarly, are no longer isolated in distinct geographic locales. Hebrew has replaced Yiddish as the primary Jewish language for many Ashkenazi Jews, although many Hasidic and Hareidi groups continue to use Yiddish in daily life. (There are numerous Ashkenazi Jewish anglophones and Russian-speakers as well, although English and Russian are not originally Jewish languages.)

France's blended Jewish community is typical of the cultural recombination that is going on among Jews throughout the world. Although France expelled its original Jewish population in the Middle Ages, by the time of the French Revolution, there were two distinct Jewish populations. One consisted of Sephardic Jews, originally refugees from the Inquisition and concentrated in the southwest, while the other community was Ashkenazi, concentrated in formerly German Alsace, and mainly speaking a German dialect similar to Yiddish. (A third community of Provenal Jews living in Comtat Venaissin were technically outside France, and were later absorbed into the Sephardim.) The two communities were so separate and different that the National Assembly emancipated them separately in 1790 and 1791.[102]

But after emancipation, a sense of a unified French Jewry emerged, especially when France was wracked by the Dreyfus affair in the 1890s. In the 1920s and 1930s, Ashkenazi Jews from Europe arrived in large numbers as refugees from antisemitism, the Russian revolution, and the economic turmoil of the Great Depression. By the 1930s, Paris had a vibrant Yiddish culture, and many Jews were involved in diverse political movements. After the Vichy years and the Holocaust, the French Jewish population was augmented once again, first by Ashkenazi refugees from Central Europe, and later by Sephardi immigrants and refugees from North Africa, many of them francophone.

Then, in the 1990s, yet another Ashkenazi Jewish wave began to arrive from countries of the former Soviet Union and Central Europe. The result is a pluralistic Jewish community that still has some distinct elements of both Ashkenazi and Sephardic culture. But in France, it is becoming much more difficult to sort out the two, and a distinctly French Jewishness has emerged.[103]

In an ethnic sense, an Ashkenazi Jew is one whose ancestry can be traced to the Jews who settled in Central Europe. For roughly a thousand years, the Ashkenazim were a reproductively isolated population in Europe, despite living in many countries, with little inflow or outflow from migration, conversion, or intermarriage with other groups, including other Jews. Human geneticists have argued that genetic variations have been identified that show high frequencies among Ashkenazi Jews, but not in the general European population, be they for patrilineal markers (Y-chromosome haplotypes) and for matrilineal markers (mitotypes).[104] Since the middle of the 20th century, many Ashkenazi Jews have intermarried, both with members of other Jewish communities and with people of other nations and faiths.[105]

A 2006 study found Ashkenazi Jews to be a clear, homogeneous genetic subgroup. Strikingly, regardless of the place of origin, Ashkenazi Jews can be grouped in the same genetic cohort that is, regardless of whether an Ashkenazi Jew's ancestors came from Poland, Russia, Hungary, Lithuania, or any other place with a historical Jewish population, they belong to the same ethnic group. The research demonstrates the endogamy of the Jewish population in Europe and lends further credence to the idea of Ashkenazi Jews as an ethnic group. Moreover, though intermarriage among Jews of Ashkenazi descent has become increasingly common, many Haredi Jews, particularly members of Hasidic or Hareidi sects, continue to marry exclusively fellow Ashkenazi Jews. This trend keeps Ashkenazi genes prevalent and also helps researchers further study the genes of Ashkenazi Jews with relative ease. It is noteworthy that these Haredi Jews often have extremely large families.[10]

The Halakhic practices of (Orthodox) Ashkenazi Jews may differ from those of Sephardi Jews, particularly in matters of custom. Differences are noted in the Shulkhan Arukh itself, in the gloss of Moses Isserles. Well known differences in practice include:

The term Ashkenazi also refers to the nusach Ashkenaz (Hebrew, "liturgical tradition", or rite) used by Ashkenazi Jews in their Siddur (prayer book). A nusach is defined by a liturgical tradition's choice of prayers, order of prayers, text of prayers and melodies used in the singing of prayers. Two other major forms of nusach among Ashkenazic Jews are Nusach Sefard (not to be confused with the Sephardic ritual), which is the general Polish Hasidic nusach, and Nusach Ari, as used by Lubavitch Hasidim.

Several famous people have Ashkenazi as a surname, such as Vladimir Ashkenazy. However, most people with this surname hail from within Sephardic communities, particularly from the Syrian Jewish community. The Sephardic carriers of the surname would have some Ashkenazi ancestors since the surname was adopted by families who were initially of Ashkenazic origins who moved to Sephardi countries and joined those communities. Ashkenazi would be formally adopted as the family surname having started off as a nickname imposed by their adopted communities. Some have shortened the name to Ash.

Relations between Ashkenazim and Sephardim have not always been warm. North African Sepharadim and Berber Jews were often looked upon by Ashkenazim as second-class citizens during the first decade after the creation of Israel. This has led to protest movements such as the Israeli Black Panthers led by Saadia Marciano a Moroccan Jew. Nowadays, relations are getting better.[107] In some instances, Ashkenazi communities have accepted significant numbers of Sephardi newcomers, sometimes resulting in intermarriage.[108][109]

Ashkenazi Jews have a noted history of achievement in Western societies[110] in the fields of exact and social sciences, literature, finance, politics, media, and others. In those societies where they have been free to enter any profession, they have a record of high occupational achievement, entering professions and fields of commerce where higher education is required.[111] Ashkenazi Jews have won a large number of the Nobel awards.[112][113] While they make up about 2% of the U.S. population,[114] 27% of United States Nobel prize winners in the 20th century,[114] a quarter of Fields Medal winners,[115] 25% of ACM Turing Award winners,[114] half the world's chess champions,[114] including 8% of the top 100 world chess players,[116] and a quarter of Westinghouse Science Talent Search winners[115] have Ashkenazi Jewish ancestry.

Time magazine's person of the 20th century, Albert Einstein,[117] was an Ashkenazi Jew. According to a study performed by Cambridge University, 21% of Ivy League students, 25% of the Turing Award winners, 23% of the wealthiest Americans, and 38% of the Oscar-winning film directors, and 29% of Oslo awardees are Ashkenazi Jews.[118]

Efforts to identify the origins of Ashkenazi Jews through DNA analysis began in the 1990s. Currently, there are three types of genetic origin testing, autosomal DNA (atDNA), mitochondrial DNA (mtDNA), and Y-chromosomal DNA (Y-DNA). Autosomal DNA is a mixture from an individual's entire ancestry, Y-DNA shows a male's lineage only along his strict-paternal line, mtDNA shows any person's lineage only along the strict-maternal line. Genome-wide association studies have also been employed to yield findings relevant to genetic origins.

Like most DNA studies of human migration patterns, the earliest studies on Ashkenazi Jews focused on the Y-DNA and mtDNA segments of the human genome. Both segments are unaffected by recombination (except for the ends of the Y chromosome the pseudoautosomal regions known as PAR1 and PAR2), thus allowing tracing of direct maternal and paternal lineages.

These studies revealed that Ashkenazi Jews originate from an ancient (2000 BCE - 700 BCE) population of the Middle East who had spread to Europe.[119] Ashkenazic Jews display the homogeneity of a genetic bottleneck, meaning they descend from a larger population whose numbers were greatly reduced but recovered through a few founding individuals. Although the Jewish people in general were present across a wide geographical area as described, genetic research done by Gil Atzmon of the Longevity Genes Project at Albert Einstein College of Medicine suggests "that Ashkenazim branched off from other Jews around the time of the destruction of the First Temple, 2,500 years ago ... flourished during the Roman Empire but then went through a 'severe bottleneck' as they dispersed, reducing a population of several million to just 400 families who left Northern Italy around the year 1000 for Central and eventually Eastern Europe."[120]

Various studies have arrived at diverging conclusions regarding both the degree and the sources of the non-Levantine admixture in Ashkenazim,[31] particularly with respect to the extent of the non-Levantine genetic origin observed in Ashkenazi maternal lineages, which is in contrast to the predominant Levantine genetic origin observed in Ashkenazi paternal lineages. All studies nevertheless agree that genetic overlap with the Fertile Crescent exists in both lineages, albeit at differing rates. Collectively, Ashkenazi Jews are less genetically diverse than other Jewish ethnic divisions, due to their genetic bottleneck.[121]

The majority of genetic findings to date concerning Ashkenazi Jews conclude that the male line was founded by ancestors from the Middle East.[122][123][124] Others have found a similar genetic line among Greeks, and Macedonians.[citation needed]

A study of haplotypes of the Y-chromosome, published in 2000, addressed the paternal origins of Ashkenazi Jews. Hammer et al.[125] found that the Y-chromosome of Ashkenazi and Sephardic Jews contained mutations that are also common among other Middle Eastern peoples, but uncommon in the autochthonous European population. This suggested that the male ancestors of the Ashkenazi Jews could be traced mostly to the Middle East. The proportion of male genetic admixture in Ashkenazi Jews amounts to less than 0.5% per generation over an estimated 80 generations, with "relatively minor contribution of European Y chromosomes to the Ashkenazim," and a total admixture estimate "very similar to Motulsky's average estimate of 12.5%." This supported the finding that "Diaspora Jews from Europe, Northwest Africa, and the Near East resemble each other more closely than they resemble their non-Jewish neighbors." "Past research found that 5080 percent of DNA from the Ashkenazi Y chromosome, which is used to trace the male lineage, originated in the Near East," Richards said.

The population has subsequently spread out. Based on accounts such as those of Jewish historian Flavius Josephus, by the time of the destruction of the Second Temple in 70 CE, as many as six million Jews were already living in the Roman Empire, but outside Israel, mainly in Italy and Southern Europe. In contrast, only about 500,000 lived in Judea, said Ostrer, who was not involved in the new study.[126]

A 2001 study by Nebel et al. showed that both Ashkenazi and Sephardic Jewish populations share the same overall paternal Near Eastern ancestries. In comparison with data available from other relevant populations in the region, Jews were found to be more closely related to groups in the north of the Fertile Crescent. The authors also report on Eu 19 (R1a) chromosomes, which are very frequent in Central and Eastern Europeans (54%60%) at elevated frequency (12.7%) in Ashkenazi Jews. They hypothesized that the differences among Ashkenazim Jews could reflect low-level gene flow from surrounding European populations or genetic drift during isolation.[127] A later 2005 study by Nebel et al., found a similar level of 11.5% of male Ashkenazim belonging to R1a1a (M17+), the dominant Y-chromosome haplogroup in Central and Eastern Europeans.[128]

Before 2006, geneticists had largely attributed the ethnogenesis of most of the world's Jewish populations, including Ashkenazi Jews, to Israelite Jewish male migrants from the Middle East and "the women from each local population whom they took as wives and converted to Judaism." Thus, in 2002, in line with this model of origin, David Goldstein, now of Duke University, reported that unlike male Ashkenazi lineages, the female lineages in Ashkenazi Jewish communities "did not seem to be Middle Eastern", and that each community had its own genetic pattern and even that "in some cases the mitochondrial DNA was closely related to that of the host community." In his view this suggested "that Jewish men had arrived from the Middle East, taken wives from the host population and converted them to Judaism, after which there was no further intermarriage with non-Jews."[104]

In 2006, a study by Behar et al.,[129] based on what was at that time high-resolution analysis of haplogroup K (mtDNA), suggested that about 40% of the current Ashkenazi population is descended matrilineally from just four women, or "founder lineages", that were "likely from a Hebrew/Levantine mtDNA pool" originating in the Middle East in the 1st and 2nd centuries CE. Additionally, Behar et al. suggested that the rest of Ashkenazi mtDNA is originated from ~150 women, and that most of those were also likely of Middle Eastern origin.[129] In reference specifically to Haplogroup K, they suggested that although it is common throughout western Eurasia, "the observed global pattern of distribution renders very unlikely the possibility that the four aforementioned founder lineages entered the Ashkenazi mtDNA pool via gene flow from a European host population".

In 2013, however, a study of Ashkenazi mitochondrial DNA by a team led by Martin B. Richards of the University of Huddersfield in England reached different conclusions, corroborating the pre-2006 origin hypothesis. Testing was performed on the full 16,600 DNA units composing mitochondrial DNA (the 2006 Behar study had only tested 1,000 units) in all their subjects, and the study found that the four main female Ashkenazi founders had descent lines that were established in Europe 10,000 to 20,000 years in the past[130] while most of the remaining minor founders also have a deep European ancestry. The study states that the great majority of Ashkenazi maternal lineages were not brought from the Near East (i.e., they were non-Israelite), nor were they recruited in the Caucasus (i.e., they were non-Khazar), but instead they were assimilated within Europe, primarily of Italian and Old French origins. Richards summarized the findings on the female line as such: "[N]one [of the mtDNA] came from the North Caucasus, located along the border between Europe and Asia between the Black and Caspian seas. All of our presently available studies including my own, should thoroughly debunk one of the most questionable, but still tenacious, hypotheses: that most Ashkenazi Jews can trace their roots to the mysterious Khazar Kingdom that flourished during the ninth century in the region between the Byzantine Empire and the Persian Empire."[126] The 2013 study estimated that 80 percent of Ashkenazi maternal ancestry comes from women indigenous to Europe, and only 8 percent from the Near East, while the origin of the remainder is undetermined.[12][130] According to the study these findings "point to a significant role for the conversion of women in the formation of Ashkenazi communities."[12][13][131][132][133][134]Karl Skorecki at Technion criticized the study for perceived flaws in phylogenetic analysis. "While Costa et al have re-opened the question of the maternal origins of Ashkenazi Jewry, the phylogenetic analysis in the manuscript does not 'settle' the question."[135]

A 2014 study by Fernndez et al. has found that Ashkenazi Jews display a frequency of haplogroup K in their maternal DNA that suggests an ancient Near Eastern origin, similar to the results of Behar. He stated that this observation clearly contradicts the results of the study led by Richards that suggested a European source for 3 exclusively Ashkenazi K lineages.[136]

In genetic epidemiology, a genome-wide association study (GWA study, or GWAS) is an examination of all or most of the genes (the genome) of different individuals of a particular species to see how much the genes vary from individual to individual. These techniques were originally designed for epidemiological uses, to identify genetic associations with observable traits.[137]

A 2006 study by Seldin et al. used over five thousand autosomal SNPs to demonstrate European genetic substructure. The results showed "a consistent and reproducible distinction between 'northern' and 'southern' European population groups". Most northern, central, and eastern Europeans (Finns, Swedes, English, Irish, Germans, and Ukrainians) showed >90% in the "northern" population group, while most individual participants with southern European ancestry (Italians, Greeks, Portuguese, Spaniards) showed >85% in the "southern" group. Both Ashkenazi Jews as well as Sephardic Jews showed >85% membership in the "southern" group. Referring to the Jews clustering with southern Europeans, the authors state the results were "consistent with a later Mediterranean origin of these ethnic groups".[10]

A 2007 study by Bauchet et al. found that Ashkenazi Jews were most closely clustered with Arabic North African populations when compared to Global population, and in the European structure analysis, they share similarities only with Greeks and Southern Italians, reflecting their east Mediterranean origins.[138][139]

A 2010 study on Jewish ancestry by Atzmon-Ostrer et al. stated "Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry", as both groups the Middle Eastern Jews and European/Syrian Jews shared common ancestors in the Middle East about 2500 years ago. The study examines genetic markers spread across the entire genome and shows that the Jewish groups (Ashkenazi and non Ashkenazi) share large swaths of DNA, indicating close relationships and that each of the Jewish groups in the study (Iranian, Iraqi, Syrian, Italian, Turkish, Greek and Ashkenazi) has its own genetic signature but is more closely related to the other Jewish groups than to their fellow non-Jewish countrymen.[140] Atzmon's team found that the SNP markers in genetic segments of 3 million DNA letters or longer were 10 times more likely to be identical among Jews than non-Jews. Results of the analysis also tally with biblical accounts of the fate of the Jews. The study also found that with respect to non-Jewish European groups, the population most closely related to Ashkenazi Jews are modern-day Italians. The study speculated that the genetic-similarity between Ashkenazi Jews and Italians may be due to inter-marriage and conversions in the time of the Roman Empire. It was also found that any two Ashkenazi Jewish participants in the study shared about as much DNA as fourth or fifth cousins.[141][142]

A 2010 study by Bray et al., using SNP microarray techniques and linkage analysis found that when assuming Druze and Palestinian Arab populations to represent the reference to world Jewry ancestor genome, between 35 and 55 percent of the modern Ashkenazi genome can possibly be of European origin, and that European "admixture is considerably higher than previous estimates by studies that used the Y chromosome" with this reference point. Assuming this reference point the linkage disequilibrium in the Ashkenazi Jewish population was interpreted as "matches signs of interbreeding or 'admixture' between Middle Eastern and European populations".[143] On the Bray et al. tree, Ashkenazi Jews were found to be a genetically more divergent population than Russians, Orcadians, French, Basques, Italians, Sardinians and Tuscans. The study also observed that Ashkenazim are more diverse than their Middle Eastern relatives, which was counterintuitive because Ashkenazim are supposed to be a subset, not a superset, of their assumed geographical source population. Bray et al. therefore postulate that these results reflect not the population antiquity but a history of mixing between genetically distinct populations in Europe. However, it's possible that the relaxation of marriage prescription in the ancestors of Ashkenazim that drove their heterozygosity up, while the maintenance of the FBD rule in native Middle Easterners have been keeping their heterozygosity values in check. Ashkenazim distinctiveness as found in the Bray et al. study, therefore, may come from their ethnic endogamy (ethnic inbreeding), which allowed them to "mine" their ancestral gene pool in the context of relative reproductive isolation from European neighbors, and not from clan endogamy (clan inbreeding). Consequently, their higher diversity compared to Middle Easterners stems from the latter's marriage practices, not necessarily from the former's admixture with Europeans.[144]

The genome-wide genetic study carried out in 2010 by Behar et al. examined the genetic relationships among all major Jewish groups, including Ashkenazim, as well as the genetic relationship between these Jewish groups and non-Jewish ethnic populations. The study found that contemporary Jews (excluding Indian and Ethiopian Jews) have a close genetic relationship with people from the Levant. The authors explained that "the most parsimonious explanation for these observations is a common genetic origin, which is consistent with an historical formulation of the Jewish people as descending from ancient Hebrew and Israelite residents of the Levant".[145]

A 2015 study by James Xue et al. results suggested that 75% of the European ancestry in AJ is South-European, with the rest mostly East European. The time of admixture was inferred to be around 30-40 generations ago, on the eve of the Ashkenazi settlement in Eastern-Europe.[146]

In the late 19th century, it was proposed that the core of today's Ashkenazi Jewry are genetically descended from a hypothetical Khazarian Jewish diaspora who had migrated westward from modern Russia and Ukraine into modern France and Germany (as opposed to the currently held theory that Jews from France and Germany migrated into Eastern Europe). The hypothesis is not corroborated by historical sources[147] and is unsubstantiated by genetics, but it is still occasionally supported by scholars who have had some success in keeping the theory in the academic conscience.[148] The theory is associated with antisemitism[149] and anti-Zionism.[150][151]

A 2013 trans-genome study carried out by 30 geneticists, from 13 universities and academies, from 9 countries, assembling the largest data set available to date, for assessment of Ashkenazi Jewish genetic origins found no evidence of Khazar origin among Ashkenazi Jews. "Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region", the authors concluded.[152]

There are many references to Ashkenazi Jews in the literature of medical and population genetics. Indeed, much awareness of "Ashkenazi Jews" as an ethnic group or category stems from the large number of genetic studies of disease, including many that are well reported in the media, that have been conducted among Jews. Jewish populations have been studied more thoroughly than most other human populations, for a variety of reasons:

The result is a form of ascertainment bias. This has sometimes created an impression that Jews are more susceptible to genetic disease than other populations.[153] Healthcare professionals are often taught to consider those of Ashkenazi descent to be at increased risk for colon cancer.[154]

Genetic counseling and genetic testing are often undertaken by couples where both partners are of Ashkenazi ancestry. Some organizations, most notably Dor Yeshorim, organize screening programs to prevent homozygosity for the genes that cause related diseases.[155][156]

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Medical genetics of Jews – Wikipedia

Thursday, December 1st, 2016

The medical genetics of Jews is the study, screening, and treatment of genetic disorders more common in particular Jewish populations than in the population as a whole.[1] The genetics of Ashkenazi Jews have been particularly well-studied, resulting in the discovery of many genetic disorders associated with this ethnic group. In contrast, the medical genetics of Sephardic Jews and Mizrahi Jews are more complicated, since they are more genetically diverse and consequently no genetic disorders are more common in these groups as a whole; instead, they tend to have the genetic diseases common in their various countries of origin.[1][2] Several organizations, such as Dor Yeshorim,[3] offer screening for Ashkenazi genetic diseases, and these screening programs have had a significant impact, in particular by reducing the number of cases of TaySachs disease.[4]

Different ethnic groups tend to suffer from different rates of hereditary diseases, with some being more common, and some less common. Hereditary diseases, particularly hemophilia, were recognized early in Jewish history, even being described in the Talmud.[5] However, the scientific study of hereditary disease in Jewish populations was initially hindered by scientific racism, which is based on racial supremacism.[6][7]

However, modern studies on the genetics of particular ethnic groups have the tightly defined purpose of avoiding the birth of children with genetic diseases, or identifying people at particular risk of developing a disease in the future.[6] Consequently, the Jewish community has been very supportive of modern genetic testing programs, although this unusually high degree of cooperation has raised concerns that it might lead to the false perception that Jews are more susceptible to genetic diseases than other groups of people.[5]

However, most populations contain hundreds of alleles that could potentially cause disease and most people are heterozygotes for one or two recessive alleles that would be lethal in a homozygote.[8] Although the overall frequency of disease-causing alleles does not vary much between populations, the practice of consanguineous marriage (marriage between second cousins or closer relatives) is common in some Jewish communities, which produces a small increase in the number of children with congenital defects.[9]

According to Daphna Birenbaum Carmeli at the University of Haifa, Jewish populations have been studied more thoroughly than most other human populations because:[10]

The result is a form of ascertainment bias. This has sometimes created an impression that Jews are more susceptible to genetic disease than other populations. Carmeli writes, "Jews are over-represented in human genetic literature, particularly in mutation-related contexts."[10] Another factor that may aid genetic research in this community is that Jewish culture results in excellent medical care, which is coupled to a strong interest in the community's history and demography.[11]

This set of advantages have led to Ashkenazi Jews in particular being used in many genetic studies, not just in the study of genetic diseases. For example, a series of publications on Ashkenazi centenarians established their longevity was strongly inherited and associated with lower rates of age-related diseases.[12] This "healthy aging" phenotype may be due to higher levels of telomerase in these individuals.[13]

The most detailed genetic analysis study of Ashkenazi was published in September 2014 by Shai Carmon and his team at Columbia University. The results of the detailed study show that today's 10 million Ashkenazi Jews descend from a population of only 350 individuals who lived about 600800 years ago. That population derived from both Europe and the Middle East.[14] There is evidence that the population bottleneck may have allowed deleterious alleles to become more prevalent in the population due to genetic drift.[15] As a result, this group has been particularly intensively studied, so many mutations have been identified as common in Ashkenazis.[16] Of these diseases, many also occur in other Jewish groups and in non-Jewish populations, although the specific mutation which causes the disease may vary between populations. For example, two different mutations in the glucocerebrosidase gene causes Gaucher's disease in Ashkenazis, which is their most common genetic disease, but only one of these mutations is found in non-Jewish groups.[4] A few diseases are unique to this group; for example, familial dysautonomia is almost unknown in other populations.[4]

TaySachs disease, which can present as a fatal illness of children that causes mental deterioration prior to death, was historically more prevalent among Ashkenazi Jews,[18] although high levels of the disease are also found in some Pennsylvania Dutch, southern Louisiana Cajun, and eastern Quebec French Canadian populations.[19] Since the 1970s, however, proactive genetic testing has been quite effective in eliminating TaySachs from the Ashkenazi Jewish population.[20]

Gaucher's disease, in which lipids accumulate in inappropriate locations, occurs most frequently among Ashkenazi Jews;[21] the mutation is carried by roughly one in every 15 Ashkenazi Jews, compared to one in 100 of the general American population.[22] Gaucher's disease can cause brain damage and seizures, but these effects are not usually present in the form manifested among Ashkenazi Jews; while sufferers still bruise easily, and it can still potentially rupture the spleen, it generally has only a minor impact on life expectancy.

Ashkenazi Jews are also highly affected by other lysosomal storage diseases, particularly in the form of lipid storage disorders. Compared to other ethnic groups, they more frequently act as carriers of mucolipidosis[23] and NiemannPick disease,[24] the latter of which can prove fatal.

The occurrence of several lysosomal storage disorders in the same population suggests the alleles responsible might have conferred some selective advantage in the past.[25] This would be similar to the hemoglobin allele which is responsible for sickle-cell disease, but solely in people with two copies; those with just one copy of the allele have a sickle cell trait and gain partial immunity to malaria as a result. This effect is called heterozygote advantage.[26]

Some of these disorders may have become common in this population due to selection for high levels of intelligence (see Ashkenazi intelligence).[27][28] However, other research suggests no difference is found between the frequency of this group of diseases and other genetic diseases in Ashkenazis, which is evidence against any specific selectivity towards lysosomal disorders.[29]

Familial dysautonomia (RileyDay syndrome), which causes vomiting, speech problems, an inability to cry, and false sensory perception, is almost exclusive to Ashkenazi Jews;[30] Ashkenazi Jews are almost 100 times more likely to carry the disease than anyone else.[31]

Diseases inherited in an autosomal recessive pattern often occur in endogamous populations. Among Ashkenazi Jews, a higher incidence of specific genetic disorders and hereditary diseases have been verified, including:

In contrast to the Ashkenazi population, Sephardic and Mizrahi Jews are much more divergent groups, with ancestors from Spain, Portugal, Morocco, Tunisia, Algeria, Italy, Libya, the Balkans, Iran, Iraq, India, and Yemen, with specific genetic disorders found in each regional group, or even in specific subpopulations in these regions.[1]

One of the first genetic testing programs to identify heterozygote carriers of a genetic disorder was a program aimed at eliminating TaySachs disease. This program began in 1970, and over one million people have now been screened for the mutation.[50] Identifying carriers and counseling couples on reproductive options have had a large impact on the incidence of the disease, with a decrease from 4050 per year worldwide to only four or five per year.[4] Screening programs now test for several genetic disorders in Jews, although these focus on the Ashkenazi Jews, since other Jewish groups cannot be given a single set of tests for a common set of disorders.[2] In the USA, these screening programs have been widely accepted by the Ashkenazi community, and have greatly reduced the frequency of the disorders.[51]

Prenatal testing for several genetic diseases is offered as commercial panels for Ashkenazi couples by both CIGNA and Quest Diagnostics. The CIGNA panel is available for testing for parental/preconception screening or following chorionic villus sampling or amniocentesis and tests for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia, Gaucher disease, mucolipidosis IV, Neimann-Pick disease type A, Tay-Sachs disease, and torsion dystonia. The Quest panel is for parental/preconception testing and tests for Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease, Neimann-Pick disease types A and B and Tay-Sachs disease.

The official recommendations of the American College of Obstetricians and Gynecologists is that Ashkenazi individuals be offered screening for Tay Sachs, Canavan, cystic fibrosis, and familial dysautonomia as part of routine obstetrical care.[52]

In the orthodox community, an organization called Dor Yeshorim carries out anonymous genetic screening of couples before marriage to reduce the risk of children with genetic diseases being born.[53] The program educates young people on medical genetics and screens school-aged children for any disease genes. These results are then entered into an anonymous database, identified only by a unique ID number given to the person who was tested. If two people are considering getting married, they call the organization and tell them their ID numbers. The organization then tells them if they are genetically compatible. It is not divulged if one member is a carrier, so as to protect the carrier and his or her family from stigmatization.[53] However, this program has been criticized for exerting social pressure on people to be tested, and for screening for a broad range of recessive genes, including disorders such as Gaucher's disease.[3]

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