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Eli Lilly cracks down on the use of weight loss drugs Mounjaro and Zepbound for cosmetic reasons instead of for diabetes and obesity  Fortune

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Transforming Corporate Health: Fitterfly's Success in Tackling Diabetes and Weight Issues  Business Standard

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Transforming Corporate Health: Fitterfly's Success in Tackling Diabetes and Weight Issues - Business Standard

Methods used to change the DNA of organisms

Genetic engineering techniques allow the modification of animal and plant genomes. Techniques have been devised to insert, delete, and modify DNA at multiple levels, ranging from a specific base pair in a specific gene to entire genes. There are a number of steps that are followed before a genetically modified organism (GMO) is created. Genetic engineers must first choose what gene they wish to insert, modify, or delete. The gene must then be isolated and incorporated, along with other genetic elements, into a suitable vector. This vector is then used to insert the gene into the host genome, creating a transgenic or edited organism.

The ability to genetically engineer organisms is built on years of research and discovery on gene function and manipulation. Important advances included the discovery of restriction enzymes, DNA ligases, and the development of polymerase chain reaction and sequencing.

Added genes are often accompanied by promoter and terminator regions as well as a selectable marker gene. The added gene may itself be modified to make it express more efficiently. This vector is then inserted into the host organism's genome. For animals, the gene is typically inserted into embryonic stem cells, while in plants it can be inserted into any tissue that can be cultured into a fully developed plant.

Tests are carried out on the modified organism to ensure stable integration, inheritance and expression. First generation offspring are heterozygous, requiring them to be inbred to create the homozygous pattern necessary for stable inheritance. Homozygosity must be confirmed in second generation specimens.

Early techniques randomly inserted the genes into the genome. Advances allow targeting specific locations, which reduces unintended side effects. Early techniques relied on meganucleases and zinc finger nucleases. Since 2009 more accurate and easier systems to implement have been developed. Transcription activator-like effector nucleases (TALENs) and the Cas9-guideRNA system (adapted from CRISPR) are the two most common.

Many different discoveries and advancements led to the development of genetic engineering. Human-directed genetic manipulation began with the domestication of plants and animals through artificial selection in about 12,000 BC.[1]:1 Various techniques were developed to aid in breeding and selection. Hybridization was one way rapid changes in an organism's genetic makeup could be introduced. Crop hybridization most likely first occurred when humans began growing genetically distinct individuals of related species in close proximity.[2]:32 Some plants were able to be propagated by vegetative cloning.[2]:31

Genetic inheritance was first discovered by Gregor Mendel in 1865, following experiments crossing peas.[3] In 1928 Frederick Griffith proved the existence of a "transforming principle" involved in inheritance, which was identified as DNA in 1944 by Oswald Avery, Colin MacLeod, and Maclyn McCarty. Frederick Sanger developed a method for sequencing DNA in 1977, greatly increasing the genetic information available to researchers.

After discovering the existence and properties of DNA, tools had to be developed that allowed it to be manipulated. In 1970 Hamilton Smiths lab discovered restriction enzymes, enabling scientists to isolate genes from an organism's genome.[4] DNA ligases, which join broken DNA together, were discovered earlier in 1967.[5] By combining the two enzymes it became possible to "cut and paste" DNA sequences to create recombinant DNA. Plasmids, discovered in 1952,[6] became important tools for transferring information between cells and replicating DNA sequences. Polymerase chain reaction (PCR), developed by Kary Mullis in 1983, allowed small sections of DNA to be amplified (replicated) and aided identification and isolation of genetic material.

As well as manipulating DNA, techniques had to be developed for its insertion into an organism's genome. Griffith's experiment had already shown that some bacteria had the ability to naturally uptake and express foreign DNA. Artificial competence was induced in Escherichia coli in 1970 by treating them with calcium chloride solution (CaCl2).[7] Transformation using electroporation was developed in the late 1980s, increasing the efficiency and bacterial range.[8] In 1907 a bacterium that caused plant tumors, Agrobacterium tumefaciens, had been discovered. In the early 1970s it was found that this bacteria inserted its DNA into plants using a Ti plasmid.[9] By removing the genes in the plasmid that caused the tumor and adding in novel genes, researchers were able to infect plants with A. tumefaciens and let the bacteria insert their chosen DNA into the genomes of the plants.[10]

The first step is to identify the target gene or genes to insert into the host organism. This is driven by the goal for the resultant organism. In some cases only one or two genes are affected. For more complex objectives entire biosynthetic pathways involving multiple genes may be involved. Once found genes and other genetic information from a wide range of organisms can be inserted into bacteria for storage and modification, creating genetically modified bacteria in the process. Bacteria are cheap, easy to grow, clonal, multiply quickly, relatively easy to transform and can be stored at -80C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria providing an unlimited supply for research.[11]

Genetic screens can be carried out to determine potential genes followed by other tests that identify the best candidates. A simple screen involves randomly mutating DNA with chemicals or radiation and then selecting those that display the desired trait. For organisms where mutation is not practical, scientists instead look for individuals among the population who present the characteristic through naturally-occurring mutations. Processes that look at a phenotype and then try and identify the gene responsible are called forward genetics. The gene then needs to be mapped by comparing the inheritance of the phenotype with known genetic markers. Genes that are close together are likely to be inherited together.[12]

Another option is reverse genetics. This approach involves targeting a specific gene with a mutation and then observing what phenotype develops.[12] The mutation can be designed to inactivate the gene or only allow it to become active under certain conditions. Conditional mutations are useful for identifying genes that are normally lethal if non-functional.[13] As genes with similar functions share similar sequences (homologous) it is possible to predict the likely function of a gene by comparing its sequence to that of well-studied genes from model organisms.[12] The development of microarrays, transcriptomes and genome sequencing has made it much easier to find desirable genes.[14]

The bacteria Bacillus thuringiensis was first discovered in 1901 as the causative agent in the death of silkworms. Due to these insecticidal properties, the bacteria was used as a biological insecticide, developed commercially in 1938. The cry proteins were discovered to provide the insecticidal activity in 1956, and by the 1980s, scientists had successfully cloned the gene that encodes this protein and expressed it in plants.[15] The gene that provides resistance to the herbicide glyphosate was found after seven years of searching in bacteria living in the outflow pipe of a Monsanto RoundUp manufacturing facility.[16] In animals, the majority of genes used are growth hormone genes.[17]

All genetic engineering processes involve the modification of DNA. Traditionally DNA was isolated from the cells of organisms. Later, genes came to be cloned from a DNA segment after the creation of a DNA library or artificially synthesised. Once isolated, additional genetic elements are added to the gene to allow it to be expressed in the host organism and to aid selection.

First the cell must be gently opened, exposing the DNA without causing too much damage to it. The methods used vary depending on the type of cell. Once it is open, the DNA must be separated from the other cellular components. A ruptured cell contains proteins and other cell debris. By mixing with phenol and/or chloroform, followed by centrifuging, the nucleic acids can be separated from this debris into an upper aqueous phase. This aqueous phase can be removed and further purified if necessary by repeating the phenol-chloroform steps. The nucleic acids can then be precipitated from the aqueous solution using ethanol or isopropanol. Any RNA can be removed by adding a ribonuclease that will degrade it. Many companies now sell kits that simplify the process.[18]

The gene researchers are looking to modify (known as the gene of interest) must be separated from the extracted DNA. If the sequence is not known then a common method is to break the DNA up with a random digestion method. This is usually accomplished using restriction enzymes (enzymes that cut DNA). A partial restriction digest cuts only some of the restriction sites, resulting in overlapping DNA fragment segments. The DNA fragments are put into individual plasmid vectors and grown inside bacteria. Once in the bacteria the plasmid is copied as the bacteria divides. To determine if a useful gene is present in a particular fragment, the DNA library is screened for the desired phenotype. If the phenotype is detected then it is possible that the bacteria contains the target gene.

If the gene does not have a detectable phenotype or a DNA library does not contain the correct gene, other methods must be used to isolate it. If the position of the gene can be determined using molecular markers then chromosome walking is one way to isolate the correct DNA fragment. If the gene expresses close homology to a known gene in another species, then it could be isolated by searching for genes in the library that closely match the known gene.[19]

For known DNA sequences, restriction enzymes that cut the DNA on either side of the gene can be used. Gel electrophoresis then sorts the fragments according to length.[20] Some gels can separate sequences that differ by a single base-pair. The DNA can be visualised by staining it with ethidium bromide and photographing under UV light. A marker with fragments of known lengths can be laid alongside the DNA to estimate the size of each band. The DNA band at the correct size should contain the gene, where it can be excised from the gel.[18]:4041 Another technique to isolate genes of known sequences involves polymerase chain reaction (PCR).[21] PCR is a powerful tool that can amplify a given sequence, which can then be isolated through gel electrophoresis. Its effectiveness drops with larger genes and it has the potential to introduce errors into the sequence.

It is possible to artificially synthesise genes.[22] Some synthetic sequences are available commercially, forgoing many of these early steps.[23]

The gene to be inserted must be combined with other genetic elements in order for it to work properly. The gene can be modified at this stage for better expression or effectiveness. As well as the gene to be inserted most constructs contain a promoter and terminator region as well as a selectable marker gene. The promoter region initiates transcription of the gene and can be used to control the location and level of gene expression, while the terminator region ends transcription. A selectable marker, which in most cases confers antibiotic resistance to the organism it is expressed in, is used to determine which cells are transformed with the new gene. The constructs are made using recombinant DNA techniques, such as restriction digests, ligations and molecular cloning.[24]

Once the gene is constructed it must be stably integrated into the genome of the target organism or exist as extrachromosomal DNA. There are a number of techniques available for inserting the gene into the host genome and they vary depending on the type of organism targeted. In multicellular eukaryotes, if the transgene is incorporated into the host's germline cells, the resulting host cell can pass the transgene to its progeny. If the transgene is incorporated into somatic cells, the transgene can not be inherited.[25]

Transformation is the direct alteration of a cell's genetic components by passing the genetic material through the cell membrane. About 1% of bacteria are naturally able to take up foreign DNA, but this ability can be induced in other bacteria.[26] Stressing the bacteria with a heat shock or electroporation can make the cell membrane permeable to DNA that may then be incorporated into the genome or exist as extrachromosomal DNA. Typically the cells are incubated in a solution containing divalent cations (often calcium chloride) under cold conditions, before being exposed to a heat pulse (heat shock). Calcium chloride partially disrupts the cell membrane, which allows the recombinant DNA to enter the host cell. It is suggested that exposing the cells to divalent cations in cold condition may change or weaken the cell surface structure, making it more permeable to DNA. The heat-pulse is thought to create a thermal imbalance across the cell membrane, which forces the DNA to enter the cells through either cell pores or the damaged cell wall. Electroporation is another method of promoting competence. In this method the cells are briefly shocked with an electric field of 10-20 kV/cm, which is thought to create holes in the cell membrane through which the plasmid DNA may enter. After the electric shock, the holes are rapidly closed by the cell's membrane-repair mechanisms. Up-taken DNA can either integrate with the bacterials genome or, more commonly, exist as extrachromosomal DNA.

In plants the DNA is often inserted using Agrobacterium-mediated recombination,[27] taking advantage of the Agrobacteriums T-DNA sequence that allows natural insertion of genetic material into plant cells.[28] Plant tissue are cut into small pieces and soaked in a fluid containing suspended Agrobacterium. The bacteria will attach to many of the plant cells exposed by the cuts. The bacteria uses conjugation to transfer a DNA segment called T-DNA from its plasmid into the plant. The transferred DNA is piloted to the plant cell nucleus and integrated into the host plants genomic DNA.The plasmid T-DNA is integrated semi-randomly into the genome of the host cell.[29]

By modifying the plasmid to express the gene of interest, researchers can insert their chosen gene stably into the plants genome. The only essential parts of the T-DNA are its two small (25 base pair) border repeats, at least one of which is needed for plant transformation.[30][31] The genes to be introduced into the plant are cloned into a plant transformation vector that contains the T-DNA region of the plasmid. An alternative method is agroinfiltration.[32][33]

Another method used to transform plant cells is biolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells or plant embryos.[34] Some genetic material enters the cells and transforms them. This method can be used on plants that are not susceptible to Agrobacterium infection and also allows transformation of plant plastids. Plants cells can also be transformed using electroporation, which uses an electric shock to make the cell membrane permeable to plasmid DNA. Due to the damage caused to the cells and DNA the transformation efficiency of biolistics and electroporation is lower than agrobacterial transformation.[citation needed]

Transformation has a different meaning in relation to animals, indicating progression to a cancerous state, so the process used to insert foreign DNA into animal cells is usually called transfection.[35] There are many ways to directly introduce DNA into animal cells in vitro. Often these cells are stem cells that are used for gene therapy. Chemical based methods uses natural or synthetic compounds to form particles that facilitate the transfer of genes into cells.[36] These synthetic vectors have the ability to bind DNA and accommodate large genetic transfers.[37] One of the simplest methods involves using calcium phosphate to bind the DNA and then exposing it to cultured cells. The solution, along with the DNA, is encapsulated by the cells.[38] Liposomes and polymers can be used as vectors to deliver DNA into cultured animal cells. Positively charged liposomes bind with DNA, while polymers can designed that interact with DNA.[36] They form lipoplexes and polyplexes respectively, which are then up-taken by the cells. Other techniques include using electroporation and biolistics.[39] In some cases, transfected cells may stably integrate external DNA into their own genome, this process is known as stable transfection.[40]

To create transgenic animals the DNA must be inserted into viable embryos or eggs. This is usually accomplished using microinjection, where DNA is injected through the cell's nuclear envelope directly into the nucleus.[26] Superovulated fertilised eggs are collected at the single cell stage and cultured in vitro. When the pronuclei from the sperm head and egg are visible through the protoplasm the genetic material is injected into one of them. The oocyte is then implanted in the oviduct of a pseudopregnant animal.[41] Another method is Embryonic Stem Cell-Mediated Gene Transfer. The gene is transfected into embryonic stem cells and then they are inserted into mouse blastocysts that are then implanted into foster mothers. The resulting offspring are chimeric, and further mating can produce mice fully transgenic with the gene of interest.[42]

Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector.[43] Genetically modified viruses can be used as viral vectors to transfer target genes to another organism in gene therapy.[44] First the virulent genes are removed from the virus and the target genes are inserted instead. The sequences that allow the virus to insert the genes into the host organism must be left intact. Popular virus vectors are developed from retroviruses or adenoviruses. Other viruses used as vectors include, lentiviruses, pox viruses and herpes viruses. The type of virus used will depend on the cells targeted and whether the DNA is to be altered permanently or temporarily.

As often only a single cell is transformed with genetic material, the organism must be regenerated from that single cell. In plants this is accomplished through the use of tissue culture.[45][46] Each plant species has different requirements for successful regeneration. If successful, the technique produces an adult plant that contains the transgene in every cell.[47] In animals it is necessary to ensure that the inserted DNA is present in the embryonic stem cells.[27] Offspring can be screened for the gene. All offspring from the first generation are heterozygous for the inserted gene and must be inbred to produce a homozygous specimen.[citation needed] Bacteria consist of a single cell and reproduce clonally so regeneration is not necessary. Selectable markers are used to easily differentiate transformed from untransformed cells.

Cells that have been successfully transformed with the DNA contain the marker gene, while those not transformed will not. By growing the cells in the presence of an antibiotic or chemical that selects or marks the cells expressing that gene, it is possible to separate modified from unmodified cells. Another screening method involves a DNA probe that sticks only to the inserted gene. These markers are usually present in the transgenic organism, although a number of strategies have been developed that can remove the selectable marker from the mature transgenic plant.[48]

Finding that a recombinant organism contains the inserted genes is not usually sufficient to ensure that they will be appropriately expressed in the intended tissues. Further testing using PCR, Southern hybridization, and DNA sequencing is conducted to confirm that an organism contains the new gene.[49] These tests can also confirm the chromosomal location and copy number of the inserted gene. Once confirmed methods that look for and measure the gene products (RNA and protein) are also used to assess gene expression, transcription, RNA processing patterns and expression and localization of protein product(s). These include northern hybridisation, quantitative RT-PCR, Western blot, immunofluorescence, ELISA and phenotypic analysis.[50] When appropriate, the organism's offspring are studied to confirm that the transgene and associated phenotype are stably inherited.

Traditional methods of genetic engineering generally insert the new genetic material randomly within the host genome. This can impair or alter other genes within the organism. Methods were developed that inserted the new genetic material into specific sites within an organism genome. Early methods that targeted genes at certain sites within a genome relied on homologous recombination (HR).[51] By creating DNA constructs that contain a template that matches the targeted genome sequence, it is possible that the HR processes within the cell will insert the construct at the desired location. Using this method on embryonic stem cells led to the development of transgenic mice with targeted knocked out. It has also been possible to knock in genes or alter gene expression patterns.[52]

If a vital gene is knocked out it can prove lethal to the organism. In order to study the function of these genes, site specific recombinases (SSR) were used. The two most common types are the Cre-LoxP and Flp-FRT systems. Cre recombinase is an enzyme that removes DNA by homologous recombination between binding sequences known as Lox-P sites. The Flip-FRT system operates in a similar way, with the Flip recombinase recognizing FRT sequences. By crossing an organism containing the recombinase sites flanking the gene of interest with an organism that expresses the SSR under control of tissue specific promoters, it is possible to knock out or switch on genes only in certain cells. This has also been used to remove marker genes from transgenic animals. Further modifications of these systems allowed researchers to induce recombination only under certain conditions, allowing genes to be knocked out or expressed at desired times or stages of development.[52]

Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the genome. The breaks are subject to cellular DNA repair processes that can be exploited for targeted gene knock-out, correction or insertion at high frequencies. If a donor DNA containing the appropriate sequence (homologies) is present, then new genetic material containing the transgene will be integrated at the targeted site with high efficiency by homologous recombination.[53] There are four families of engineered nucleases: meganucleases,[54][55] ZFNs,[56][57] transcription activator-like effector nucleases (TALEN),[58][59] the CRISPR/Cas (clustered regularly interspaced short palindromic repeat/CRISPRassociated protein (e.g. CRISPR/Cas9).[60][61] Among the four types, TALEN and CRISPR/Cas are the two most commonly used.[62] Recent advances have looked at combining multiple systems to exploit the best features of both (e.g. megaTAL that are a fusion of a TALE DNA binding domain and a meganuclease).[63] Recent research has also focused on developing strategies to create gene knock-out or corrections without creating double stranded breaks (base editors).[62]

Meganucleases were first used in 1988 in mammalian cells.[64] Meganucleases are endodeoxyribonucleases that function as restriction enzymes with long recognition sites, making them more specific to their target site than other restriction enzymes. This increases their specificity and reduces their toxicity as they will not target as many sites within a genome. The most studied meganucleases are the LAGLIDADG family. While meganucleases are still quite susceptible to off-target binding, which makes them less attractive than other gene editing tools, their smaller size still makes them attractive particularly for viral vectorization perspectives.[65][53]

Zinc-finger nucleases (ZFNs), used for the first time in 1996, are typically created through the fusion of Zinc-finger domains and the FokI nuclease domain. ZFNs have thus the ability to cleave DNA at target sites.[53] By engineering the zinc finger domain to target a specific site within the genome, it is possible to edit the genomic sequence at the desired location.[65][66][53] ZFNs have a greater specificity, but still hold the potential to bind to non-specific sequences.. While a certain amount of off-target cleavage is acceptable for creating transgenic model organisms, they might not be optimal for all human gene therapy treatments.[65]

Access to the code governing the DNA recognition by transcription activator-like effectors (TALE) in 2009 opened the way to the development of a new class of efficient TAL-based gene editing tools. TALE, proteins secreted by the Xanthomonas plant pathogen, bind with great specificity to genes within the plant host and initiate transcription of the genes helping infection. Engineering TALE by fusing the DNA binding core to the FokI nuclease catalytic domain allowed creation of a new tool of designer nucleases, the TALE nuclease (TALEN).[67] They have one of the greatest specificities of all the current engineered nucleases. Due to the presence of repeat sequences, they are difficult to construct through standard molecular biology procedure and rely on more complicated method of such as Golden gate cloning.[62]

In 2011, another major breakthrough technology was developed based on CRISPR/Cas (clustered regularly interspaced short palindromic repeat / CRISPR associated protein) systems that function as an adaptive immune system in bacteria and archaea. The CRISPR/Cas system allows bacteria and archaea to fight against invading viruses by cleaving viral DNA and inserting pieces of that DNA into their own genome. The organism then transcribes this DNA into RNA and combines this RNA with Cas9 proteins to make double-stranded breaks in the invading viral DNA. The RNA serves as a guide RNA to direct the Cas9 enzyme to the correct spot in the virus DNA. By pairing Cas proteins with a designed guide RNA CRISPR/Cas9 can be used to induce double-stranded breaks at specific points within DNA sequences. The break gets repaired by cellular DNA repair enzymes, creating a small insertion/deletion type mutation in most cases. Targeted DNA repair is possible by providing a donor DNA template that represents the desired change and that is (sometimes) used for double-strand break repair by homologous recombination. It was later demonstrated that CRISPR/Cas9 can edit human cells in a dish. Although the early generation lacks the specificity of TALEN, the major advantage of this technology is the simplicity of the design. It also allows multiple sites to be targeted simultaneously, allowing the editing of multiple genes at once. CRISPR/Cpf1 is a more recently discovered system that requires a different guide RNA to create particular double-stranded breaks (leaves overhangs when cleaving the DNA) when compared to CRISPR/Cas9.[62]

CRISPR/Cas9 is efficient at gene disruption. The creation of HIV-resistant babies by Chinese researcher He Jiankui is perhaps the most famous example of gene disruption using this method.[68] It is far less effective at gene correction. Methods of base editing are under development in which a nuclease-dead Cas 9 endonuclease or a related enzyme is used for gene targeting while a linked deaminase enzyme makes a targeted base change in the DNA.[69] The most recent refinement of CRISPR-Cas9 is called Prime Editing. This method links a reverse transcriptase to an RNA-guided engineered nuclease that only makes single-strand cuts but no double-strand breaks. It replaces the portion of DNA next to the cut by the successive action of nuclease and reverse transcriptase, introducing the desired change from an RNA template.[70]

Excerpt from:
Genetic engineering techniques - Wikipedia

Genetic engineering is the alteration of an organisms genotype using recombinant DNA technology to modify an organisms DNA to achieve desirable traits. The addition of foreign DNA in the form of recombinant DNA vectors generated by molecular cloning is the most common method of genetic engineering. The organism that receives the recombinant DNA is called a genetically modified organism (GMO). If the foreign DNA that is introduced comes from a different species, the host organism is called transgenic. Bacteria, plants, and animals have been genetically modified since the early 1970s for academic, medical, agricultural, and industrial purposes. In the US, GMOs such as Roundup-ready soybeans and borer-resistant corn are part of many common processed foods.

Although classical methods of studying the function of genes began with a given phenotype and determined the genetic basis of that phenotype, modern techniques allow researchers to start at the DNA sequence level and ask: What does this gene or DNA element do? This technique, called reverse genetics, has resulted in reversing the classic genetic methodology. This method would be similar to damaging a body part to determine its function. An insect that loses a wing cannot fly, which means that the function of the wing is flight. The classical genetic method would compare insects that cannot fly with insects that can fly, and observe that the non-flying insects have lost wings. Similarly, mutating or deleting genes provides researchers with clues about gene function. The methods used to disable gene function are collectively called gene targeting. Gene targeting is the use of recombinant DNA vectors to alter the expression of a particular gene, either by introducing mutations in a gene, or by eliminating the expression of a certain gene by deleting a part or all of the gene sequence from the genome of an organism.

The process of testing for suspected genetic defects before administering treatment is called genetic diagnosis by genetic testing. Depending on the inheritance patterns of a disease-causing gene, family members are advised to undergo genetic testing. For example, women diagnosed with breast cancer are usually advised to have a biopsy so that the medical team can determine the genetic basis of cancer development. Treatment plans are based on the findings of genetic tests that determine the type of cancer. If the cancer is caused by inherited gene mutations, other female relatives are also advised to undergo genetic testing and periodic screening for breast cancer. Genetic testing is also offered for fetuses (or embryos with in vitro fertilization) to determine the presence or absence of disease-causing genes in families with specific debilitating diseases.

Gene therapy is a genetic engineering technique used to cure disease. In its simplest form, it involves the introduction of a good gene at a random location in the genome to aid the cure of a disease that is caused by a mutated gene. The good gene is usually introduced into diseased cells as part of a vector transmitted by a virus that can infect the host cell and deliver the foreign DNA (Figure (PageIndex{1})). More advanced forms of gene therapy try to correct the mutation at the original site in the genome, such as is the case with treatment of severe combined immunodeficiency (SCID).

Traditional vaccination strategies use weakened or inactive forms of microorganisms to mount the initial immune response. Modern techniques use the genes of microorganisms cloned into vectors to mass produce the desired antigen. The antigen is then introduced into the body to stimulate the primary immune response and trigger immune memory. Genes cloned from the influenza virus have been used to combat the constantly changing strains of this virus.

Antibiotics are a biotechnological product. They are naturally produced by microorganisms, such as fungi, to attain an advantage over bacterial populations. Antibiotics are produced on a large scale by cultivating and manipulating fungal cells.

Recombinant DNA technology was used to produce large-scale quantities of human insulin in E. coli as early as 1978. Previously, it was only possible to treat diabetes with pig insulin, which caused allergic reactions in humans because of differences in the gene product. Currently, the vast majority of diabetes sufferers who inject insulin do so with insulin produced by bacteria.

Human growth hormone (HGH) is used to treat growth disorders in children. The HGH gene was cloned from a cDNA library and inserted into E. coli cells by cloning it into a bacterial vector. Bacterial HGH can be used in humans to reduce symptoms of various growth disorders.

Although several recombinant proteins used in medicine are successfully produced in bacteria, some proteins require a eukaryotic animal host for proper processing. For this reason, the desired genes are cloned and expressed in animals, such as sheep, goats, chickens, and mice. Animals that have been modified to express recombinant DNA are called transgenic animals. Several human proteins are expressed in the milk of transgenic sheep and goats, and some are expressed in the eggs of chickens. Mice have been used extensively for expressing and studying the effects of recombinant genes and mutations.

Manipulating the DNA of plants (i.e., creating GMOs) has helped to create desirable traits, such as disease resistance, herbicide and pesticide resistance, better nutritional value, and better shelf-life (Figure (PageIndex{3})). Plants are the most important source of food for the human population. Farmers developed ways to select for plant varieties with desirable traits long before modern-day biotechnology practices were established.

Plants that have received recombinant DNA from other species are called transgenic plants. Because they are not natural, transgenic plants and other GMOs are closely monitored by government agencies to ensure that they are fit for human consumption and do not endanger other plant and animal life. Because foreign genes can spread to other species in the environment, extensive testing is required to ensure ecological stability. Staples like corn, potatoes, and tomatoes were the first crop plants to be genetically engineered.

Gene transfer occurs naturally between species in microbial populations. Many viruses that cause human diseases, such as cancer, act by incorporating their DNA into the human genome. In plants, tumors caused by the bacterium Agrobacterium tumefaciens occur by transfer of DNA from the bacterium to the plant. Although the tumors do not kill the plants, they make the plants stunted and more susceptible to harsh environmental conditions. Many plants, such as walnuts, grapes, nut trees, and beets, are affected by A. tumefaciens. The artificial introduction of DNA into plant cells is more challenging than in animal cells because of the thick plant cell wall.

Researchers used the natural transfer of DNA from Agrobacterium to a plant host to introduce DNA fragments of their choice into plant hosts. In nature, the disease-causing A. tumefaciens have a set of plasmids, called the Ti plasmids (tumor-inducing plasmids), that contain genes for the production of tumors in plants. DNA from the Ti plasmid integrates into the infected plant cells genome. Researchers manipulate the Ti plasmids to remove the tumor-causing genes and insert the desired DNA fragment for transfer into the plant genome. The Ti plasmids carry antibiotic resistance genes to aid selection and can be propagated in E. coli cells as well.

Bacillus thuringiensis (Bt) is a bacterium that produces protein crystals during sporulation that are toxic to many insect species that affect plants. Bt toxin has to be ingested by insects for the toxin to be activated. Insects that have eaten Bt toxin stop feeding on the plants within a few hours. After the toxin is activated in the intestines of the insects, death occurs within a couple of days. Modern biotechnology has allowed plants to encode their own crystal Bt toxin that acts against insects. The crystal toxin genes have been cloned from Bt and introduced into plants. Bt toxin has been found to be safe for the environment, non-toxic to humans and other mammals, and is approved for use by organic farmers as a natural insecticide.

The first GM crop to be introduced into the market was the Flavr Savr Tomato produced in 1994. Antisense RNA technology was used to slow down the process of softening and rotting caused by fungal infections, which led to increased shelf life of the GM tomatoes. Additional genetic modification improved the flavor of this tomato. The Flavr Savr tomato did not successfully stay in the market because of problems maintaining and shipping the crop.

Unless otherwise noted, images on this page are licensed under CC-BY 4.0 by OpenStax.

OpenStax, Biology. OpenStax CNX. May 27, 2016 http://cnx.org/contents/s8Hh0oOc@9.10:8CA_YwJq@3/Cloning-and-Genetic-Engineerin

Moen I, Jevne C, Kalland K-H, Chekenya M, Akslen LA, Sleire L, Enger P, Reed RK, Oyan AM, Stuhr LEB. 2012.Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation.BMC Cancer. 12:21. doi:10.1186/1471-2407-12-21 PDF

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20.3: Genetic Engineering - Biology LibreTexts

What is Integrative Medicine?

Integrative medicine (IM) is an emerging field that emphasizes the evidence-basedcombination of both conventional and alternative approaches to address the biological, psychological, social and spiritual aspects of health and illness.

Integrative Medicine practitioners usually take a holistic/total person approach to their patients. They understand that overall health and well-being is a combination of multiple factors, including genetics, physiology, the environment, personal relationships, health beliefs, and the power of a positive medical interaction. In some situations, Integrative Medicine modalities may achieve similar results to conventional medicine with fewer side effects, and may create a greater sense of individual self-efficacy.

Stanford contains an Integrative Medicine Center; hospital-wide functions such as massage and pet therapy; various clinic-specific programs; educators and researchers exploring integrative medicine; and individual practitioners who may be either trained in, or knowledgeable about and open to, various modalities.

The purpose of this website is to gather together in one place an easily accessible snapshot of where to find Integrative Medicine modalities and practitioners/researchers/educators at Stanford Medical Center. It will be regularly updated. If you find something missing, please contact the webmaster.

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Integrative Medicine | Stanford Medicine

Despite spending more than double on health care per citizen than most industrialized nations, the U.S. nears the bottom of the top 40 nations in health system rankings.Integrative & Lifestyle Medicine can change that.

Definition from the Academic Consortium of Integrative Medicine and Health: Integrative medicine and health reaffirms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic and lifestyle approaches, healthcare professionals and disciplines to achieve optimal health and healing.

An Integrative Health practitioner uses all appropriate therapies, both conventional and complementary, to facilitate healing and promote optimal health. In the past several decades, the United States has seen a dramatic increase in morbidity from preventable illnesses such as obesity, heart disease, cancer and diabetes.

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People today want to take responsibility for their well-being by addressing the effects of lifestyle, emotions, and social interactions on health. People with certain health conditions can greatly benefit from an integrative approach to care. Some of these conditions include:

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Definition from the American College of Lifestyle Medicine: Lifestyle medicine is a medical specialty that uses therapeuticlifestyleinterventions as a primary modality to treat chronic conditionsincluding,but not limited to,cardiovascular diseases, type 2 diabetes, and obesity.Lifestyle medicine-certified clinicians are trained to applyevidence-based,whole-person, prescriptive lifestyle change to treat and, when used intensively, often reverse such conditions. Applying the six pillars of lifestyle medicinea whole-food, plant-predominant eating pattern, physical activity, restorative sleep, stress management, avoidance of risky substances and positive social connectionsalso provides effective prevention for these conditions.

The American College of Lifestyle Medicine (ACLM)is the medical professional society for physicians and other professionals dedicated to clinical and worksite practice of lifestyle medicine as the foundation of a transformed and sustainable health care system.

Lifestyle medicine can address up to 80% of chronic diseases. A lifestyle medicine approach to population care has the potential to arrest the decades-long rise in the prevalence of chronic conditions and their burdensome costs. Patient and provider satisfaction often results from a lifestyle medicine approach, which strongly aligns the field with the Quintuple Aim of better health outcomes, lower cost, improved patient satisfaction, improved provider well-being, and advancement of health equity, in addition to its alignment with planetary health. Lifestyle medicine is the foundation for a redesigned, value-based and equitable healthcare delivery system, leading to whole person health.

Medical Sciences Building Suite 4358231 Albert Sabin WayPO Box 670582Cincinnati, OH 45267-0582

Mail Location: 0582Phone: 513-558-2310Fax: 513-558-3266Email: osher.integrative@uc.edu

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What is Integrative & Lifestyle Medicine - UC Cincinnati

The Integrative Medicine Service provides evidence-based complementary therapies to improve our patients experiences, physical outcomes, emotional wellness, and quality of life.

Our diverse multidisciplinary team includes medicine, acupuncture, massage therapy, creative arts therapies, mind-body therapies, and exercise. We offer a patient-centered approach that evaluates and helps people manage the emotional burden of their diagnosis and complications that arise from cancer treatment.

Our team of experts provides nurturing therapies that address chronic issues such as pain, neuropathy, fatigue and insomnia, stress, anxiety, mobility, and more.

Since 1999, our Integrative Medicine Service has been leading the field in innovative, patient-centered research. Our doctors and researchers studying how integrative therapies can be used to better control or reduce the side effects of cancer treatment.

Through activities like fellowships, onsite training programs, online courses, and our award-winning About Herbs library, we teach and train health care providers about best clinical practices, and the value of integrative medicine in cancer care.

About HerbsExplore MSKs award-winning About Herbs online library and mobile app for objective information on the potential benefits and risks of using dietary supplements and herbal products.

Continuing Education& TrainingOur online continuing education courses and onsite training opportunities prepare doctors, acupuncturists, nurses, and integrative health specialists to practice evidence-based integrative cancer care in their local community. MSK faculty members design every program with your needs and those of people with cancer everywhere in mind.

Refer a PatientFind out how to refer a patient to MSKs team of integrative medicine doctors and therapists, who provide a spectrum of care to people with cancer.

Research & Clinical TrialsDiscover how MSK helps move the field of integrative oncology forward through high-quality studies, many of which are open at any given time.

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Integrative Medicine Service - Memorial Sloan Kettering Cancer Center

Integrative medicine includes the full spectrum of physical, emotional, mental, social, spiritual, and environmental factors that influence your health. This comprehensive, customized, whole-person approach to health care is beneficial, whether you want to maintain optimal health or you are coping with an ongoing condition. In both cases, our services improve how your physical body interacts with your psychological and emotional well-being.

A Place to RelaxDuke Integrative Medicine Centers healing environment features spa-like amenities including a whirlpool, sauna, steam room, meditation spaces, walking labyrinth, library, quiet room, contemplative gardens, and more. Our spacious, wood-paneled front hall sits at the edge of Duke Forest and is surrounded by floor-to-ceiling windows. Wait for your appointments in our comfortable waiting rooms.

Our circular library features relaxing, leather seating, and a soaring, cathedral ceiling. Our sun-drenched quiet room is filled with bamboo that stretches to reach the glass walls high above. Use our transition rooms to prepare for fitness activities, acupuncture, massage, and one-on-one yoga sessions.

Attend our many programs, workshops,and professional training in our spaces designed for large gatherings.

Our Environmentally-Conscious FacilityThe Duke Integrative Medicine Center is a 27,000-square-foot facility on the Duke Center for Living Campus, at the edge of Duke Forest and near Duke University Hospitaland Duke Clinic. Our spaces are available to Duke groups for rental.

Our building was designed in line with our commitment to conservation and sustainability. We were the first Leadership in Energy and Environmental Design (LEED) certified medical building in North Carolina.

We Are Committed to Education and TrainingPart of our mission is to educate a new generation of health professionals to provide integrative approaches that benefit their patients.

We Offer Clinical TrialsThrough our partnerships, you may have access to clinical trials that will help provide more information about elements of integrative medicine and their impacts over time.

Our Leaders Are Nationally RecognizedOur providers are also nationally recognized leaders who are using new models of medicine, education, and research to help shape the future of health care.

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Duke Integrative Medicine Center | Durham, NC | Duke Health

You have 20/20 vision if you can find the hidden chick amongst these ducks  IndiaTimes

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You have 20/20 vision if you can find the hidden chick amongst these ducks - IndiaTimes

Raha Kapoor's blue eyes remind fans of her great-grandfather, Raj Kapoor; here's what genetics says  IndiaTimes

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Raha Kapoor's blue eyes remind fans of her great-grandfather, Raj Kapoor; here's what genetics says - IndiaTimes

The question of how to live a long, healthy life is increasingly at the forefront of medical research. While centuries ago some may have turned to finding mythical immortality-granting items like the Holy Grail, scientists now say that achieving longevity may rely on eating the right foods, adopting healthy habits, and remaining socially active.

Reaching your hundredth birthday means you become a member of a special club of centenarians. While researchers believe the number of centenarians was very low before 1900, today many more people are able to reach this ripe old age.

As of 2021, there were an estimated 573,000 centenarians globally. The United Nations expects that number to jump rapidly, with a reported estimate of 3.7 million by 2050.

What do centenarians do to help them reach triple-digit birthdays what is their secret? Medical News Today spoke with six experts to find out what the secret sauce behind longevity is.

In 2016, National Geographic Fellow Dan Buettner and his team published a study on what they found to be the secrets to longevity.

Dubbed the Blue Zones, Buettner identified five specific areas of the world where people consistently live over 100 years of age. These areas are:

These are places where human beings have lived manifestly longest, Buettner explained to Medical News Today. Theyve achieved the health outcomes we want: long lives largely free of chronic disease. Since only 80% of how long we live is dictated by disease, these peoples lifestyles and environments offer us instructions and clues for how we can set up our lives to live longer.

Within these five areas, Buettner discovered there were nine common practices that people followed that might explain their slower aging process. Called the Power 9, they include:

Loneliness, said Buettner, is a top risk factor for a shorter life, so preventing that as much as we can could help add years to our lives:

We know that lonely people are expected to live 8 fewer years than well-connected people and that health behaviors [are] measurably contagious. People in Blue Zones are in socially connected villages with strong social ties, which gives them a longevity edge from the very beginning.

Theres no short-term fix [or] supplement for longevity, he added. Learn plant-based dishes that you like and cook at home. Curate a social circle of three to five healthy friends [who] will care about you on a bad day. Health behaviors are contagious, and friends tend to be long-term adventures.

As diet makes up a few of the Power 9 learned from Blue Zones, Buettner has also launched the Blue Zone Food Guidelines that feature 11 recommendations reflecting how the worlds longest-living people ate for most of their lives.

If you want to know what a centenarian [did to live] to be 100, you have to know what they ate during their whole [life], he said. Working with Harvard for my book The Blue Zones Kitchen, we collected 155 dietary studies done in all Blue Zones over the past 80 years and averaged them.

It was clear that over 90% of their traditional dietary intake came from whole food, plant-based sources [and] was about 65% complex carbs, noted Buettner. The pillars of every longevity diet in the world are whole grains, nuts, greens, and other garden vegetables, tubers, and beans.

Dr. Valter Longo, Edna M. Jones Chair in Gerontology and professor of gerontology and biological sciences at the USC Leonard Davis School of Gerontology, developed the Longevity Diet after years of research into aging, nutrition, and disease.

The Longevity Diet, based on [the] five pillars of longevity, entails all of the everyday and periodic dietary habits that are associated with increased longevity and healthspan, he explained to MNT.

The main facets of the Longevity Diet include:

Because diet [is] intended as how and what we eat and not as a method to lose weight, [it] can regulate the genes that regulate the aging process, but also those that regulate the removal of damaged components of cells and the regeneration of parts of various tissues and organs, Dr. Longo added.

Additionally, previous research suggests that the Mediterranean diet can also provide benefits when it comes to longevity.

A review published in January 2020 concluded that the Mediterranean diet helps slow down the progression of aging and the onset of frailty in older age.

And research published in March 2021 says adhering to the Mediterranean diet may add years to a persons life.

According to Monique Richard, a registered dietitian nutritionist, owner of Nutrition-In-Sight in Johnson City, TN, and national media spokesperson for the Academy of Nutrition and Dietetics, when it comes to eating for longevity, diets like the Blue Zone Diet, Longevity Diet, and Mediterranean diet stand out because of the lifestyle components they share.

Examples of commonalities observed within these populations include more families and individuals growing and consuming their food [and] eating more whole foods, as in closest to what Mother Nature has made versus derived from a manufacturing plant, industrial farm, or fast food chain, she explained to MNT.

Overall intake and composition of these diets include less highly-processed foods, therefore often automatically decreasing levels of sodium, artificial flavors, colorings, and preservatives, fats or added sugar. Richard noted.

These dietary patterns often include foods lower in saturated fats, cholesterol, and calories, including more foods that are richer in nutrients such as fiber, antioxidants like vitamin C, E, A, [and] B, and higher in minerals such as potassium, magnesium, and iodine.

Monique Richard

When looking to make diet changes to increase longevity, Richard said it is not just about extending life, but also about increasing its quality.

She suggested:

The emphasis is not on restriction or negative consequences, but leaning into true quality, consistency, and overall health with a pillar of foundational pure, wholesome factors, Richard said.

Dont forget to slow down with eating, with chewing, with making or creating a meal, with making time to stop and smell the flowers, [and] with making long-lasting meaningful changes, she added.

The power of positive thinking is known to be beneficial to a persons overall mental health. However, previous research shows that a positive attitude may even help a person live longer.

A study published in August 2019 found that being optimistic was associated with a person living 11-15% longer and having a stronger likelihood of living to age 85 or older.

Research published in October 2022 suggested that positive-thinking women in an ethnically diverse United States population lived an average of 4.4 years more than those who did not think positively.

Having a positive, optimistic outlook reduces our risk for developing chronic diseases and gives us a greater chance of living past 85, Dr. Karen D. Sullivan, a board-certified neuropsychologist and owner of I CARE FOR YOUR BRAIN in Pinehurst, NC explained to MNT.

The mechanism behind these benefits is thought to be related to the protection optimism offers against the inflammatory damage of stress. Studies on negative emotions show a weakening effect on the immune system.

Dr. Karen D. Sullivan

Additionally, Dr. Karen Miller, a neuropsychologist, geropsychologist, and senior director of the Brain Wellness and Lifestyle Programs at Pacific Neuroscience Institute in Santa Monica, CA, noted that inflammation caused by stress is one of the culprits leading to more rapid aging, more physical difficulties, and more cognitive difficulties.

So when were thinking positive and engaging in positive behaviors, such as [] meditation, yoga, participating in our own personal religious practices, getting out and walking, exercising, [or] enjoying the fresh air, all those things are bringing down our stress and bringing down our level of inflammation, she continued.

If were under a lot of stress were going to have higher inflammation and higher inflammation actually can cause cellular damage to our bodies, particularly our brains, Dr. Miller noted.

In addition to staying positive and participating in activities that help lower stress, remaining socially active and connected to other humans has also been associated with living a long life.

A study published in September 2019 found women who had strong social relationships had a 10% longer life span and 41% better chance of living to age 85.

And research published in May 2023 showed that frequent participation in social activity was significantly associated with prolonged overall survival in older adults.

We are social beings with a social brain we are wired to be part of a group with needs for both contributing value and being valued, Dr. Sullivan explained.

People who identify as lonely have a [] greater risk of dying early than those who feel satisfied with their social life. The chronic stress of loneliness weakens our immune systems, making us more susceptible to infectious diseases and chronic diseases, especially cardiovascular disease and cancer.

Dr. Karen D. Sullivan

When actively socializing, Dr. Miller said, we are engaging in cognitive stimulation that helps keep the brain engaged and healthy.

When we are involved with another person, there is that volley, that give and take, she told MNT. Its like a tennis match the ideas are going back and forth. And that type of cognitive stimulation actually inspires our brains to be more mentally agile, or like what we like to think of in neuropsychology as cognitive flexibility.

Plus, conversing and engaging with others helps you learn more information, think creatively, and stimulate problem-solving skills, resulting in what Dr. Miller referred to as a whole-brain workout.

That type of engagement, that social stimulation, is what I would call natures brain bootcamp, she added. Were literally engaging in bootcamp for our brain where were socializing, which is very different than if I was isolated and I didnt have that opportunity.

While experts agree a healthy diet, limiting stress, thinking positively, and staying socially active can potentially lead to a longer life, there are some other healthy habits that are also important.

For example, smoking can take years off your life. A study published in June 2020 found that not smoking and being socially engaged throughout older age were common in centenarians free from common chronic diseases.

Keeping a healthy weight is also important for longevity. Research published in 2017 concluded that a high body mass index (BMI) was associated with substantially shorter healthy and chronic disease-free life expectancy.

Regular exercise can also help you live longer. A study published in August 2022 found that light or moderate to vigorous physical activity were both associated with a lower risk of mortality in older women, while higher sedentary time increased their mortality risk.

Several studies have shown that physical activity is associated with lower risk of mortality in older adults, Dr. Aladdin Shadyab, associate professor of epidemiology at the Herbert Wertheim School of Public Health & Human Longevity Science at UC San Diego, and senior author of the study told MNT.

We were the first to show that higher levels of physical activity and lower time spent sedentary are associated with reduced risk of mortality, irrespective of having genes that predispose to a long life. These findings overall highlight the importance of maintaining a physically active lifestyle in old age to achieve longevity, said Dr. Shadyab.

I think maintaining a healthy diet and engaging in regular exercise is most important, particularly for older adults, he added. Even light activities, such as walking, are important for maintaining a long and healthy life in the aging population.

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Longevity: What lifestyle habits could help you live to 100?

Helen Mongelia's 102 years reflect the mysterious alchemy of genetic, environmental, and lifestyle factors that coalesce to aid longevity. Fresh food, consistent movement, emotional resilience, and a family full of long-living relatives mark the centenarian's colorful life span, which began in 1919 while Woodrow Wilson occupied the White House.

Longevity like Mrs. Mongelia's remains extraordinary, with an estimated one in 6,000 people in the United States reaching 100 nowadays, according to the U.S. Administration on Aging. More than 100,000 were 100 or older in 2019, triple the number in 1980 who'd passed their 100th birthday.

Scientists, including those at Harvard, are eagerly studying people in their 90s and beyond to tease out what contributes to exceptionally long living. People enduring to extreme old age often have lifestyles that fuel vigor and hamper age-related chronic diseases such as heart disease, cancer, and diabetes. They typically are nonsmokers, are not obese, and cope effectively with stress, according to the National Institutes of Health (NIH). Most are women.

"I didn't expect to live this long, that's for sure," says Mrs. Mongelia, who lived independently until 101 when she also gave up driving and happily holds a mailroom job at her assisted living residence in Connecticut. "But I've tried not to let anything bother me too much. I have two great daughters, two sons-in-law, and two grandchildren what else can you ask for? There's my happiness right there."

Mrs. Mongelia never restricted her diet, eating meat but skipping most alcoholic drinks. But her early fare as the middle child of 11 was abundant in fruits and vegetables, many grown in her family's garden in Carbondale, Pa., and canned to enjoy all year long. The large clan also walked "everywhere," trekking miles round-trip to church, school, and the grocery store.

Mrs. Mongelia's healthy habits hit a sweet spot that science increasingly spotlights as optimal for longevity. A new Harvard-led study spanning 11 years and involving 2,400 people (average age 60; 55% women) suggests that a Mediterranean diet rich in fruits, vegetables, and healthy fats may dampen inflammation and prevent age-related frailty, a major predictor of decline affecting between 10% and 15% of older adults.

"Frailty is hard to define, but it's really easy to spot. In general, it's a state of increased vulnerability," says Courtney Millar, a postdoctoral research fellow at the Marcus Institute for Aging Research at Harvard-affiliated Beth Israel Deaconess Medical Center.

"It's important to focus on frailty prevention and treatment, because it's associated with so many of the factors that determine someone's longevity," says Millar, a co-author of the study, published online May 12, 2022, by The American Journal of Clinical Nutrition.

Another new study suggests that young adults who begin optimizing their diets at age 20 by veering from typical Western fare to more whole grains, legumes, and nuts could increase their life expectancy by more than a decade. Published online Feb. 8, 2022, by PLOS Medicine, the study posited that people who start such dietary shifts even at age 60 can still reap substantial benefits, increasing life expectancy by eight years for women; 80-year-olds could gain another three-plus years.

"I'm certainly a believer that food is medicine," Millar says, "and there's some great evidence that dietary factors can improve longevity."

Mrs. Mongelia's family is peppered with relatives who've had far longer-than-average life spans. Although her coal miner father died of black lung disease at 78, Mrs. Mongelia's mother lived to 93, and many siblings also thrived into their 10th decade. Two brothers still survive.

Research reinforces this link: siblings and children of long-living people are more likely to live beyond peers and remain healthier while doing so, according to the NIH. A study published online May 28, 2022, by The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences suggested that children of those who reach 100 carry a specific "genetic footprint" explaining why they're less frail than peers whose parents were not centenarians.

Might our genes be the linchpin to longevity? "My take is that it's certainly a combination of lifestyle and genetics," Millar says. "Certain dietary factors and even exercise regimens can modify how our genes are expressed and contribute to what's going on in our bodies. It's a really important intersection of our health."

Some scientists use the term "biohacks" to refer to tweaks in daily habits and choices that aim to tamp down inflammation and blunt aging's effects. Many of these tactics aren't new, but Harvard experts say that employing them consistently might contribute to longevity.

Move more. Vigorous movement has repeatedly been linked with lower risks of heart disease, diabetes, obesity, and other chronic health problems.

Review your health history. Talk to your primary care doctor about your health conditions and any new symptoms so you can manage them appropriately.

Try intermittent fasting. Compressing meals into a six- or eight-hour window each day boosts the body's natural process of eliminating damaged cells and proteins, lowering inflammation levels.

Eat a plant-forward diet. Antioxidants from fruits and vegetables and fiber from whole grains all help to lower inflammation levels. Beans, chickpeas, and other legumes were hailed as a key dietary predictor of longevity in a study that found a daily dietary increase of just 20 grams (less than an ounce) of legumes lowers our risk of dying in any given year by 8%.

Boost your outlook. List your life goals and imagine a future where they've been reached, or think about three good things that happened to you every day. Write them down.

Despite a hardscrabble path that included dropping out of school after 11th grade to take care of a baby sibling and also working as a button operator in a dress factory where she earned three cents per dozen buttons mounted Mrs. Mongelia maintains an upbeat attitude that matches her hardy body. She relies on a walker and hearing aids, but remains mentally sharp. "Just keep going and going and going, and don't give up," she counsels.

A recent Harvard-led analysis of nearly 160,000 American women linked positive outlook to extended life span. Published online June 8, 2022, by the Journal of the American Geriatrics Society, the study analyzed data and survey responses from women who were 50 to 79 years old when they enrolled in the study in the 1990s. The researchers then tracked participants' survival for up to 26 years. The results suggested that higher levels of optimism correlated with higher odds of living beyond 90.

About a quarter of the relationship between optimism and living longer may reflect health-related factors such as eating healthy foods, controlling weight, exercising, and limiting alcohol, says study co-author Dr. Hayami Koga, a researcher and doctoral candidate in population health sciences at the Harvard T.H. Chan School of Public Health.

The findings hint at the value of focusing on positive psychological factors as possible new ways of promoting longevity and healthy aging, Dr. Koga says. "There's some evidence that optimistic people are more likely to have goals and the confidence to reach them," she adds. "I think it drives people to be more confident and take actions that lead to better health."

Photo by Timothy H. Cole

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Aiming for longevity - Harvard Health

As medical and social advances mitigate diseases of old age and prolong life, the number of exceptionally long-lived people is increasing sharply. The United Nations estimates that there were about 95,000 centenarians in 1990 and more than 450,000 in 2015. By 2100, there will be 25 million. Although the proportion of people who live beyond their 110th birthday is far smaller, this once-fabled milestone is also increasingly common in many wealthy nations. The first validated cases of such supercentenarians emerged in the 1960s. Since then, their global numbers have multiplied by a factor of at least 10, though no one knows precisely how many there are. In Japan alone, the population of supercentenarians grew to 146 from 22 between 2005 and 2015, a nearly sevenfold increase.

Given these statistics, you might expect that the record for longest life span would be increasing, too. Yet nearly a quarter-century after Calments death, no one is known to have matched, let alone surpassed, her 122 years. The closest was an American named Sarah Knauss, who died at age 119, two years after Calment. The oldest living person is Kane Tanaka, 118, who resides in Fukuoka, Japan. Very few people make it past 115. (A few researchers have even questioned whether Calment really lived as long as she claimed, though most accept her record as legitimate based on the weight of biographical evidence.)

As the global population approaches eight billion, and science discovers increasingly promising ways to slow or reverse aging in the lab, the question of human longevitys potential limits is more urgent than ever. When their work is examined closely, its clear that longevity scientists hold a wide range of nuanced perspectives on the future of humanity. Historically, however and somewhat flippantly, according to many researchers their outlooks have been divided into two broad camps, which some journalists and researchers call the pessimists and the optimists. Those in the first group view life span as a candle wick that can burn for only so long. They generally think that we are rapidly approaching, or have already reached, a ceiling on life span, and that we will not witness anyone older than Calment anytime soon.

In contrast, the optimists see life span as a supremely, maybe even infinitely elastic band. They anticipate considerable gains in life expectancy around the world, increasing numbers of extraordinarily long-lived people and eventually, supercentenarians who outlive Calment, pushing the record to 125, 150, 200 and beyond. Though unresolved, the long-running debate has already inspired a much deeper understanding of what defines and constrains life span and of the interventions that may one day significantly extend it.

The theoretical limits on the length of a human life have vexed scientists and philosophers for thousands of years, but for most of history their discussions were largely based on musings and personal observations. In 1825, however, the British actuary Benjamin Gompertz published a new mathematical model of mortality, which demonstrated that the risk of death increased exponentially with age. Were that risk to continue accelerating throughout life, people would eventually reach a point at which they had essentially no chance of surviving to the next year. In other words, they would hit an effective limit on life span.

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How Long Can We Live? - The New York Times

SALT LAKE CITY, Dec. 21, 2023 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc., (NASDAQ: MYGN), a leader in genetic testing and precision medicine, today announced the appointment of Scott Leffler as Chief Financial Officer (CFO), effective January 29, 2024. Leffler will succeed Myriad CFO Bryan Riggsbee who is retiring. Riggsbee will continue as a strategic advisor through March 31, 2024, to ensure a smooth transition.

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Myriad Genetics Chief Financial Officer Bryan Riggsbee Retires; Scott Leffler Appointed as Successor; Reiterates Previously Issued Financial Guidance

Next phase of multi-million-dollar project to include scaling up cGMP manufacturing for phase 1 trial targeting infectious disease

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NightHawk Biosciences Announces Completion of Demonstration Run for a Top-Tier NIH and DTRA Funded Research University

NEW YORK, Dec. 21, 2023 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune modulating therapeutic cancer vaccines based on its T-win® platform, announced today that the first patient has been dosed in its Phase 2 trial (NCT05280314) studying treatment with IO102-IO103 in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in neoadjuvant and adjuvant patients with resectable melanoma or squamous cell carcinoma of the head and neck (SCCHN) before and after surgery with curative intent.

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IO Biotech Announces First Patient Dosed in Phase 2 Neoadjuvant/Adjuvant Solid Tumor Basket Trial

-- SynAIRgy Compares AD109 to Placebo Over 6 Months in People with OSA who Are Intolerant of or Refuse Positive Airway Pressure (PAP) Therapy, the Current Standard of Care

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Apnimed Announces First Patient Dosed in SynAIRgy, the Second Phase 3 Clinical Study of AD109, a Potential Nighttime Oral Treatment for Obstructive...

New System Saves Time and Resources, Improves Efficiency and Accuracy New System Saves Time and Resources, Improves Efficiency and Accuracy

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Cytek® Biosciences Introduces the Cytek Orion™ Reagent Cocktail Preparation System, the First-of-its-Kind Automated Cocktail Preparation Instrument...

MINNEAPOLIS, Dec. 21, 2023 (GLOBE NEWSWIRE) --  Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, today announced it has entered into agreements with certain holders of its existing warrants exercisable for 2,556,000 shares of its common stock, in the aggregate, to exercise outstanding warrants at the existing exercise price of $0.78 per share, in exchange for new warrants as described below. The aggregate gross proceeds from the exercise of the existing warrants is expected to total approximately $2.0 million, before deducting financial advisory fees. The exercisability of the new warrants and any resulting issuance of the shares underlying the new warrants are subject to stockholder approval in accordance with Nasdaq rules.

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Panbela Therapeutics Announces Exercise of Warrants and Issuance of New Warrants in a Private Placement for $2.0 Million Gross Proceeds Priced...

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Mithra and Rafa Laboratories sign binding Head of Terms to commercialize DONESTA® in Israel