StemCell Therapy

by Ben Best CONTENTS: LINKS TO SECTIONS BY TOPIC

Often we see people who smoke, don't exercise and eat all the wrong foods living to be a ripe old age. People tell us that it doesn't matter whether you smoke or are overweight, what matters is having good genes. Is this true?

The simple answer is that for every elderly person who is overweight, smokes, doesn't exercise, eats the wrong foods and doesn't take supplements there are many more who lived the same lifestyle and are in the cemetery (and who are therefore less visible). There are also many more people the same age who are living a more healthy lifestyle (emphasis on "living") and who are more healthy. Good heredity can protect you from bad living somewhat, but you are better off to live well.

(return to contents)

The longest, largest and most authoritative study on the effects of smoking upon health and longevity has followed the lives of nearly 35,000 British physicians since 1951[BRITISH MEDICAL JOURNAL; Doll,R; 328(7455):1519-1528 (2004)]. Although physicians may not seem representative of the population in general, their health histories and causes of death are very well documented.

Claims have been made that smokers die earlier than nonsmokers due to more risk-taking personalities, rather than because of the effects of tobacco. True enough, heavy smokers (over 25 cigarettes per day) in the study died of accidents, injury and poisoning more than twice as often as nonsmokers (in a couple of cases from fires started while smoking in bed). But these deaths accounted for less than 3% of total mortality.

According to the study, a heavy smoker is about 25 times more likely to die of lung cancer than a nonsmoker. And a light smoker (1 to 14 cigarettes per day) is about 8 times more likely to die of lung cancer. Similarly, a heavy smoker is about 24 times more likely to die of chronic obstructive pulmonary disease than a nonsmoker and a light smoker is about 9 times more likely. A similar relationship is seen for death rates from other forms of cancer and respiratory disease. This close relationship between fatal lung disease and smoking makes it difficult to deny that the smoke is directly damaging to the lungs.

On average, the nonsmokers lived about 10 more years than the smokers. For those born between 1920 and 1929 the death rate between the ages of 35 and 69 for nonsmokers was 15% and for smokers was 43% nearly three times greater. Of course, the smokers who survived beyond age 69 probably had better genes than those who did not, but they undoubtedly suffered more from respiratory disease and other forms of illness than the surviving nonsmokers.

The British physician study results are very similar to a survey of nearly a million American men and women by the American Cancer Society[AMERICAN JOURNAL OF PUBLIC HEALTH; Taylor,DH; 92(6):990-996 (2002)].

(return to contents)

(For more detail, see Health Benefits of Exercise)

Many studies have shown an association between exercise and reduced incidence of heart disease, adult onset diabetes and even cancer. A study of nearly 45,000 male health professionals showed that those who exercised in the highest 25% of intensity had a risk of coronary heart disease that was 70% that seen among the lowest 25%[JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Tanasescu,M; 288(16):1994-2000 (2002)]. A study of nearly 22,000 male physicians showed that men who exercised 2 to 4 times weekly had 80% the stroke rate of those who exercised less than once per week[STROKE; Lee,IM; 30(1):1-6 (1999)]. A study of over 72,000 nurses showed that the fifth of women who exercised the most had 66% the stroke risk of the fifth who exercised the least. The middle fifth had 82% of the stroke risk of the fifth who exercised the least25%[JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Hu,FB; 283(22):2961-2967 (2000)].

Diabetes increases the incidence of a variety of health conditions, including heart disease, neuropathy, kidney failure, etc. increasing the likelihood of an early death. In many ways diabetes exhibits the features of accelerated aging. "Type2 diabetes" also called "non-insulin-dependent diabetes" was formerly called "adult onset diabetes". But adolescents have increasingly been developing the disease. A Cincinnati study showed a ten-fold increase in adolescent type2 diabetes in the period between 1982 and 1994[THE JOURNAL OF PEDIATRICS; Pinhas-Hamiel,O; 128(5Pt1):608-615 (1996)]. There was not a ten-fold change in genetic makeup of adolescents in that period, but there was a great increase in adolescent obesity. A study of nearly 85,000 nurses concluded that obesity is the single most important factor leading to type2 diabetes in women[NEW ENGLAND JOURNAL OF MEDICINE; Hu,FB; 345(11):790-797 (2001)] (a result which is probably valid for men as well).

A study of nearly 22,000 male physicians showed that those who exercised more than 5times weekly had only 58% the incidence of type2 diabetes as those who exercised less than once per week. Those who exercised two to four times weekly had 62% the diabetes incidence and those who exercised once weekly had 77% the incidence[JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Manson,JE; 268(1):63-67 (1992)]. Someone could argue that those who chose to exercise were those who are less likely to get diabetes, but a study which randomly assigned 3,234 non-diabetic persons to exercise at least 150 minutes per week or to not exercise showed those who exercised were only 58% as likely to get type2 diabetes as those who did not[NEW ENGLAND JOURNAL OF MEDICINE; Knowler,WC; 346(6):393-403 (2002)].

Even cancer risk might be reduced by exercise. An extensive review of the literature found a high relationship for both colorectal cancer and breast cancer with lack of exercise[CANCER CAUSES AND CONTROL; McTiernan,A; 9(5):487-508 (1998)]. Breast cancer and colorectal cancer are significantly influenced by diet as well as by exercise. A study in Italy found a correlation between these forms of cancer and the intake of saturated (but not polyunsaturated) fat[ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY; Favero,A; 492:51-55 (1999)].

(return to contents)

(For more detail, see Macronutrients, Dieting and Health)

A study of nearly 40,000 women health professionals found that the fifth who consumed the most dietary fiber had 46% the risk of myocardial infarction and 65% the total cardiovascular disease risk of the fifth consuming the least dietary fiber[JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY; Liu,S; 39(1):49-56 (2002)].

A study of Seventh Day Adventists showed that those who observed a vegetarian diet were at least four times less likely to have high blood pressure than those who ate meat[JOURNAL OF HYPERTENSION; Rouse,IL; 1(1):65-71 (2002)]. About a third of California Seventh Day Adventists are vegetarians, and those vegetarians have been shown to live 9.5 years (men) or 6.1 years (women) longer than other Californians. High blood pressure can cost 4.2 years (men) or 3.2 years (women) and diabetes (which is usually very susceptible to influence by diet) can cost 4.6 years (men) or 8.6 years (women)[ARCHIVES OF INTERNAL MEDICINE; Fraser,GE; 161(13):1645-1652 (2001)]. A prospective study of over half-a-million people found elevated mortality, cancer mortality and cardiovascular disease mortality in those who at red meat and processed meat (sausage, hot dogs, etc.)[ARCHIVES OF INTERNAL MEDICINE; Sinha,R; 169(6):562-571 (2009)].

The literature abounds with evidence that diets rich in fruits and vegetables reduce the risk of cancer and cardiovascular disease[JOURNAL OF POSTGRADUATE MEDICINE; Heber,D; 50(2):145-149 (2004)]. Diet certainly has an influential effect on longevity which is separable from heredity.

Caloric Restriction with Adequate Nutrition (CRAN) dramatically extends the maximum lifespan of laboratory animals. Rats, mice and hamsters experience maximum lifespan extension from a diet which contains 4060% of the calories (but all of the required nutrients) which the animals consume when they can eat as much as they want. Mean lifespan is increased over 50% and maximum lifespan is increased over 30%. There is evidence that humans on CRAN experience similar benefits. The experimental animals in these studies are compared to genetically-matched controls which eat freely and experience no life extension benefits. The dramatic diffenece in lifespan is due to diet, not genes.

The composition of protein, carbohydrate and fat in the diet can also significantly affect health and longevity. For details on this subject, see my essay Macronutrients, Dieting and Health.

(return to contents)

(For more detail, see Nutraceuticals Topic Index )

What about nutritional supplements? Poor nutrition is common, especially in the elderly. Supplements consisting of recommended dietary allowances of nutrients (plus extra VitaminE & beta-carotene) significantly improved the immune status of elderly subjects[THE LANCET 340:1124-1127 (1992)]. In fact, a randomized, double-blind placebo-controlled study of 200IU supplementation with alpha-tocopherol in persons over 65 years of age showed a 20% reduction in incidence of the common cold[JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Meydani,SN; 292(7):828-836 (2004)].

In 1996 the JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION published the results of a multi-center, double-blind, randomized, placebo-controlled cancer prevention trial based on 200g/day selenium or placebo to 1,312 patients over a mean period of 4.5years[JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Clark,LC; 276(24):1957-1963 (1996)]. The study reported a 50% decrease in total cancer incidence as well as a 63% reduction in prostate cancer, a 58% reduction in colorectal cancer and a 48% reduction in lung cancer. Only 6 of the 1,312 subjects had selenium blood levels below that achievable by the RDA prior to supplementation. Not only was this study a powerful refutation of the claim that dietary supplements are of no benefit, but its results were so impactful that it would be unethical for anyone to repeat it. After extensive scrutiny of the data only the evidence for reduction of prostate cancer is now accepted as statistically significant (for a 42% reduction in prostate cancer). The data still shows a total cancer mortality reduction of 51%[CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION; Duffield-Lillico,AJ; 11(7):630-639 (2002)].

It is worth noting the recent efforts of Dr. Bruce Ames to promote the use of supplements. Bruce Ames is most famous for the "Ames Test" which has allowed researchers to use bacteria rather than lab animals to screen for potential cancer-causing agents thus expediting the screening process. Dr. Ames says that it is unreasonable to expect that everyone (particularly the poor) is going to eat the recommended five servings of fruits and vegetables every day. He not only advocates a general vitamin and mineral supplement as an "insurance policy" to ensure getting the recommended minimums, but advises that recommended minimums are not sufficient to provide maximum protection from disease. And he notes the regenerative potential of taking supplements that combine lipoic acid with acetyl-L-carnitine[EMBO REPORTS; Ames,BN; 6(SpecNo):S20-S24 (2005)].

AntiOxidants and other supplements are excessively disparaged by some biogerontologists on the grounds that they do not increase maximum lifespan. But significantly increasing average age of death can be a gain in both life and health. The Nutraceuticals section of this website provides a great deal of evidence that nutritional supplements can improve health and thereby increase average lifespan ("square the curve").

(return to contents)

In Western countries, females live about 10% longer than males. Males have 4times as much oxidative DNA damage as females, presumably because females have more MnSOD and glutathione peroxidase[FREE RADICAL BIOLOGY & MEDICINE; Borras,C; 34(5):546-552 (2003)]. A 2002 study of centenarians in the United States found that female siblings were 8times more likely to reach age100 than cohorts born the same year and male siblings were 17times for likely to become centenarians themselves[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Perls,TT; 99(12):8442-8447 (2002)]. Mothers of persons who lived to at least 110years ("supercentenarians") were nearly six times more likely to have lived to age90 than females in the general population[JOURNAL OF GERONTOLOGY; Perls,T; 62A(9):1028-1034 (2007)]. Studies of centenarian populations have found quite a number of longevity-associated genotypes[PLoS GENETICS; Martin,GM; 3(7):e125 (2007)].

Children of older fathers (within the age range 25 to 45) were found to have longer telomeres and greater resistance to mortality from aging-associated diseases[AGING CELL; Unryn,BM; 4(2):97-101 (2005)]. A ten-year study of Danish twins aged 73-94 found a positive correlation between leucocyte telomere length and expected lifespan[AMERICAN JOURNAL OF EPIDEMIOLOGY; Kimura,M; 167(7):799-806 (2008)]. Studies of sperm from young(<30years) and old(>50years) donors found that sperm telomerase length increases with age[PLOS GENETICS; Kimura,M; 4(2):e37 (2008)].

Male sperm are produced throughtout life, whereas a woman typically produces few, if any, new egg cells during her reproductive years. For this reason, a mother typically passes about 14mutations to her offspring, whereas a father will pass about 40mutations at age20 and 80mutations at age40. Mutations in the father increase exponentially with age, doubling about every 16.5years[NATURE;Kong,A; 488:471-475 (2012)]. Risk of diseases such as autism and schizophrenia in offspring rise with increasing age of the father[Ibid.].

The cause of death for a sample 143 people over the age of 60 with shorter telomeres was found to be several times greater for heart disease and infectious diseases, but not for cancer[THE LANCET; Cawthon,RM; 361:393-395 (2003)]. Another study showed a significant correlation between telomere shortening and cognative impairment in elderly subjects[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Canela,A; 104(12):5300-5305 (2007)]. Yet another study found an inverse relationship between telomere length and pulse pressure, indicating a possible direct relationship between vascular aging and telomere length[HYPERTENSION; Jeanclos,E; 36(2):195-200 (2000)]. In a cohort of coronary artery disease outpatients the rate of telomere shortening was inversely related to blood levels of omega-3 polyunsaturated fatty acids[JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION; Farzaneh-Far,R; 303(3):250-257 (2010)]. Higher levels of oxidative stress due to environmental factors increase the rate of telomere shortening[TRENDS IN BIOCHEMICAL SCIENCES 27(7):339-344 (2002)]. Psychological stress may be one of the environmental factors[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Epel,ES; 101(49):17312-17315 (2004)]. A study of 175 elderly Swedish twin-pairs found that the twins with the shortest telomeres (75% of the cohort) had 3times the risk of death compared to the 25% with the longest telomeres[AGING CELL; Bakaysa,SL; 6(6):769-774 (2007)].

Identical twins (monozygotic twins) have the same heredity (identical genes), so differences in the health and longevity of identical twins can only be due to environmental factors. Of course, identical twins typically have similar environments. Fraternal twins are also born together, are no closer genetically than other siblings, and have environments which are probably as similar as those shared by identical twins. Thus, comparing identical twins with fraternal twins can be a way of determining which effects are due to heredity and which are due to lifestyle (environment).

A study of Scandinavian twins found that if a female lived to be at least 92years, a fraternal twin had 1.57 the chance of doing so, and an identical twin was 2.5times more likely to do so than other females. For males, a fraternal twin was 1.76times as likely to reach 92 and an identical twin was 4.83times as likely[HUMAN GENETICS; Hjelmborg,J; 119(3):312-321 (2006)].

Both fraternal and identical twins show correlated levels of the inflammatory cytokines Tumor Necrosis Factor-alpha(TNF) and IL6 which play a role in diabetes and metabolic syndrome indicative of the influence of a common environment, including the intrauterine environment. Nonetheless, elderly twins show a strong genetic component to their plasma TNF levels[DIABETOLOGIA; Grunnet,L; 49(2):343-350 (2006)]. A study of 80-year-olds found that serum IL6 levels predicted mortality for both males & females, but TNF only predicted mortality for males[CLINICAL &; EXPERIMENTAL IMMUNOLOGY; Bruunsgaard,H; 132(1):24-31 (2003)]. But another study found serum TNF to predict mortality in centenarians, whereas IL6, IL8 and CRP did not[AMERICAN JOURNAL OF MEDICINE; Bruunsgaard,H; 115(4):278-283 (2003)].

Female centenarians are significantly more likely to have a gene that reduces IGF1 receptor signalling[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Suh,Y; 105(9):3438-3442 (2008)]. Two copies of a FOXO3A allele tripled the odds of becoming a centenarian in a Japanese-American cohort[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Willcox,BJ; 105(37):13987-13992 (2008)].

A long-term study of twins in Denmark showed that when one fraternal twin had a fatal stroke, there was a 10% chance that the other fraternal twin would die of stroke. But for identical twins there was an 18% chance that the second twin would also die of a stroke[STROKE; Bak,S; 33(3):769-774 (2002)]. The fact that identical twins (who have exactly the same genes) would be nearly twice as likely to have a stroke as fraternal twins (who are no closer genetically than any brother or sister) indicates that heredity does play a role in the likelihood of having a stroke. Nonetheless, the fact that when one of two genetically identical twins has a stoke that there is a less than 20% chance that the second genetically identical twin will have a stroke indicates that at least 80% of the chance of having a stroke is due to environmental (lifestyle) factors.

The Framingham Longevity Study showed that age at death can be predicted much better by Coronary Heart Disease (CHD) risk factors than risk factors for stroke or cancer[JOURNAL OF CLINICAL EPIDEMIOLOGY; Brand,FN; 45(2):169-174 (1992)]. A study of nearly 21,000 Swedish twins[JOURNAL OF INTERNAL MEDICINE; 252(3):247-254 (2002)] showed that when one male twin died of CHD there was a 57% likelihood that the other male twin would also die of CHD. Insofar as only about 20% of males normally die of CHD (roughly half of all male deaths due to cardiovascular disease are due to CHD), 57% represents nearly 3 times the frequency that would be expected between randomly selected pairs of men. Although this represents a significant role for heredity in CHD death for men, the fact that 43% of male twins die of causes different from the CHD that killed the first twin indicates a significant role for lifestyle in causing CHD death.

For female twins only in 38% of cases did the second twin die of CHD when the first twin had died of CHD. This would seem to indicate that for women, lifestyle rather than heredity more strongly influences the chance of dying from CHD than is the case for men. However, the study noted that the older twins were when they died, the less likely it would be for both twins to die of the same cause. In other words, the longer you live, the more your cause of death will be determined by your lifestyle rather than by your heredity. Women normally live longer than men, so by dying at a greater age their causes of death are more influenced by lifestyle and less influenced by heredity than is the case for men. If men had lived longer, we would expect greater differences in cause of death between the male twins.

Divergence of twins with age is not only evident in lifestyle factors such as smoking, exercise, diet and environment, but in gene expression. A study which compared 3-year-old identical twins with 50-year-old identical twins found that the younger twins were very epigenetically similar, whereas the older twins were very distinct in epigenetic expression[PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA); Fraga,MF; 102(30):10604-10809 (2005)]. A study on mice showed that alterations in epigenetic expression with age may be up to two orders of magnitude greater than somatic mutations[GENETICS; Bennett-Baker,PE; 165(4):2055-2062 (2003)].

(return to contents)

Good genes do make a difference in being healthy and living long, but lifestyle choices usually make a bigger difference. And the longer we life, the more our remaining longevity depends upon our lifestyle rather than on our genes. The choice is not between quantity (long life) and quality (good health), because good health is usually a requirement for living long. Whether your genes are good or bad, you will probably be more healthy as well as live longer by not smoking, by exercising and by eating a good diet (which can be augmented by supplements).

(return to contents)

HOME PAGE

Read the original post:
Is Longevity Entirely Hereditary? - BEN BEST

This entry was posted on August 4, 2016 at 9:40 am and is filed under Longevity Genetics. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |