Relevant for Civil Services Pre & Main

Intervention in Human Cycle: Possibility of Age Reversing

What is xenotransplantation ? What are the factors sharing an impact on human aging? What is HGH?
Anti-aging, experimental gerontology, and biomedical gerontology, refers to attempts to slow down or reverse the processes of aging to extend both the maximum and average lifespan. Some researchers in this area, believe that future breakthroughs in tissue rejuvenation with stem cells, molecular repair, and organ replacement (such as with artificial organs or xenotransplantation) will eventually enable humans to have indefinite lifespan through complete rejuvenation to a youthful condition. Aging has been defined as the collection of changes that render human beings progressively more likely to die. At present, the biological basis of ageing is unknown. Most scientists agree that substantial variability exists in the rates of ageing across different species, and that this to a large extent is genetically based. In model organisms and laboratory settings, researchers have been able to demonstrate that selected alterations in specific genes can extend lifespan (quite substantially in nematodes, less so in fruit flies, and even less in mice). Nevertheless, even in the relatively simple organisms, the mechanism of aging remains to be elucidated. Because the lifespan of even the simple lab mouse is around 3 years, very few experiments directly test specific ageing theories. The US National Institute on Aging currently funds an intervention testing program, whereby investigators nominate compounds (based on specific molecular ageing theories) to have evaluated with respect to their effects on lifespan and age-related biomarkers in outbred mice. Previous age-related testing in mammals has proved largely irreproducible, because of small numbers of animals, and lax mouse husbandry conditions. The sale of putative anti-aging products such as nutrition, physical fitness, skin care, hormone replacements, vitamins, supplements and herbs is a lucrative global industry, with the US market generating about $50 billion of revenue each year. Medical experts state that the use of such products has not been shown to affect the aging process. During the process of aging, an organism
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accumulates damage to macromolecules, cells, tissues and organs. The maximum life span for human is in excess of 120 years, whereas the maximum lifespan of a mouse commonly used as a model in research on aging, is about four years. Genetic differences between humans and mice that may account for these different aging rates include efficiency of DNA repair, types and quantities of antioxidant enzymes, and different rates of free radical production. Average lifespan in a population is lowered by infant and child mortality, which are frequently linked to infectious diseases or nutrition problems. Later in life, vulnerability to accidents and age-related chronic disease such as cancer or cardiovascular disease play an increasing role in mortality. Extension of expected lifespan can often be achieved by good diet, exercise and avoidance of hazards such as smoking. Maximum lifespan is determined by the rate of aging for a species inherent in its genes and by environmental factors. One widely recognized method of extending maximum lifespan in organisms such as nematodes is calorie restriction. Another technique used evolutionary pressure such as breeding from only older members. Theoretically, extension of maximum lifespan could be achieved by reducing the rate of aging damage, by periodic replacement of damaged tissues, or by molecular repair or rejuvenation of deteriorated cells and tissues. Factors That Have Impact on Human Aging Process:

Hormonal therapies
Many hormones levels go down with age. Some of the oldest and still most popular anti-aging treatments emerged based on the assumption that hormonal changes are important in aging. The most famous of these involves human growth hormone (HGH). Growth hormone has been used as an anti-aging treatment for a long time and some evidence suggests HGH has beneficial effects in elderly people. HGH supplements might increase muscle mass, strengthen the immune system, increase libido, etc. There are studies in elderly

similar class of compounds is aimed at quenching ROS patients in which they claim to feel younger after HGH treatment. While HGH was once hailed as a major production in mitochondria. These can include not breakthrough, like many other anti-aging products, it only antioxidants but products that allegedly failed to live up to expectations, in part because of its rejuvenate mitochondria by optimizing metabolism negative side-effects. The most serious side effect is or membrane potential. Like for many other products, probably cancer. Although HGH is not mutagenic, it however, none of these products has been proven to makes cancer grow, which means that if you have a have any effect on aging, either in animal models or in cancer and take HGH, the cancer will spread faster. humans. Other side-effects might include weight gain, high ALT-711 blood pressure, diabetes, etc. ALT-711 is one of the latest anti-aging compounds Insulin-like growth factor 1 (IGF-1) is another to receive worldwide attention. It acts by catalytically hormone that may play a role in aging and can be breaking AGE crosslink: Advanced Glycosylation Endpurchased as a dietary supplement. Like GH, IGF-1s product crosslink occur when glucose is attached to a levels decline with age and, in mice, low levels of IGFprotein, like it can happen in arteries. For this, ALT1 appear to correlate with longevity; mutations in mice 711 seems to be useful against heart disease by that lower IGF-1 seem to reducing pulse pressure and extend lifespan. What is IGF-1? improving arterial elasticity. Other hormones whose The full effects and sideproduction decreases with What is DHEA? effects of this drug are still age include unknown but it seems like a What are Antioxidants? Dehydroepiandrosterone promising intervention to (DHEA) and melatonin. What is Anti-aging Medicine ameliorate agings effects, DHEA has been reported to though it probably does not improve the well being of the What is ALT-711 delay aging as a whole. elderly by a variety of ways: Diets and supplements improved memory, immune system, muscle mass, Much life extension research focuses on nutrition sexual appetite, and benefits to the skin. Protection diets or supplementsas a means to extend lifespan, against cancer has also been argued but some types of although few of these have been systematically tested cancernamely prostate and breast canceractually for significant longevity effects. The many diets appear to increase with DHEA. Minor side effects such promoted by anti-aging advocates are often as acne have also been reported. contradictory. Two diets with different approaches and Melatonin is a hormone mostly involved in sleep some support from scientific research are the Paleolithic and circadian rhythms, the latter hypothesized by diet and Caloric restriction. some to be associated with aging and life-extension. The free radical theory of aging suggests that Finally, for women, estrogen is a popular anti-aging antioxidant supplements, such as Vitamin C, therapy. This hormone is generally used in conjunction Vitamin E, Q10, lipoic acid, Carnosine and Nwith others in hormone replacement therapy. It does acetylcysteine, might extend human life. However, reduce the effects of menopause protecting against heart combined evidence from several clinical trials suggests disease and osteoporosis that high dose Vitamin E and beta carotene supplements increase mortality rates. Other substances Antioxidants proposed to extend lifespan include oxytocin, insulin, One theory of aging is the free radical theory of human chorionic gonadotropin (hCG) and aging. Succinctly, when oxygen is used to make energy erythropoietin (EPO). Resveratrol is a sirtuin stimulant in human cells, it releases reactive compounds called that appears to extend lifespan in simple model free radicals or reactive oxygen species (ROS). To fight organisms such as nematodesand short-lived fish. ROS, cells possess an array of defenses called Some supplements, including the minerals antioxidants many of which can be synthesized or seleniumor zinc have been reported to extend the extracted, purified, and then sold, generally in tablets, lifespan of rats and mice, though none has been proven as anti-aging drugs. Common antioxidants include to do so in humans, and significant toxic effects were vitamins A, C, and E and co-enzyme Q10. Fortunately, observed. there is probably little if nothing wrong with taking these products as serious side-effects have not been Anti Aging Medicine described. Unfortunately, there is little evidence any of Several drugs and food supplements have been these products actually work. In mice, for instance, shown to retard or reverse the biological effects of many studies indicate that antioxidants do not slow ageing in animal models; none has yet been proven to aging although they can slightly increase longevity. do so in humans. Since one major source of ROS is mitochondria, a Resveratrol, a chemical found in red grapes, has
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been shown to extend the lifespan of yeast by 60%, improper cell functioning, senescence, and genetic worms and flies by 30% and one species of fish by abnormalities. These changes make cell more and more almost 60%. It does not extend the lifespan of healthy sensitive towards cellular decline. mice but delays the onset of age-related disease and Hormesis infirmity. It works by enabling the gene SRT-1 which Various genes whose products and interactions mimics the effect of calorie restriction, which in some creates homeodynamic space based upon the different animals has been shown to lengthen lifespan. repair mechanisms like free radical scavenging, protein Small doses of heavy water increase fruit-fly turn over regulation, detoxification, stress and immune lifespan by 30%, but large doses are toxic to complex response, DNA damage repair and many more. This organisms. space determines the chance of survival and In 2002, a team led by Professor Bruce Ames at UC maintenance, if any contraction in this space leads to Berkeley discovered that feeding aged rats a aging and related diseases. combination of acetyl-L-carnitine and alpha-lipoic Role of Klotho gene in endothelial dysfunction acid (both substances are Klotho gene possibly already approved for human What are the genetic and cellular factors that provides protection to use and sold in health food cardiac system by enhancing affect aging process? stores) produced a nitric oxide production as rejuvenating effect. What is the role of Kiotho gene in endothetical? well as by decreasing In 2007, researchers at oxidative stress due to free the Salk Institute for What is Co-enzime Q? radicals. Human klotho Biological Studies, identified gene present mainly in a critical gene in nematode worms that specifically kidney. Deficiency of gene causes several aging related links eating fewer calories with living longer. Professor conditions; on the other hand, over-expression can Andrew Dillin and colleagues showed that the increase the life span in mammals by 20-30%. Klotho gene pha-4 regulates the longevity response to calorie found useful in regulating endothelial dysfunction. restriction. In the same year Dr Howard Chang of Klotho is emerging as very important anti-aging gene. the Stanford University School of Medicine was able to Co-enzyme Q and aging rejuvenate the skin of two-year-old mice to resemble Co-enzyme is a small molecule (not a protein but that of newborns by blocking the activity of the sometimes a vitamin) essential for the activity of some gene NF-kappa-B. enzymes. The role of coenzyme Q (Q) in cellular In 2009, a drug called rapamycin, discovered in the respiration is crucial. It is also one of essential factor 1970s in the soil of Easter Island in the South Pacific, in various important systems in cell like respiratory was found to extend the life expectancy of 20-monthtransport chain (in mitochondria), antioxidant part old mice by up to 38%.Rapamycin is generally used to (cell membrane) and redox homeostasis (cell) which suppress the immune system and prevent the rejection shows its influence on aging process and related of transplanted organs. degenerations. Deficiency of Q level associated with Also in 2009, the British Journal of Nutrition decreased activity of mitochondria and free radical reported a study at Tufts University in Boston which defense (as Q requires in these processes) results in showed that brain function and motor skills in aged various aging related neurogenerative diseases. As rats could be improved by adding walnuts to their diet. Muscular system and CNS shows poor incorporation The human equivalent would be to eat seven to nine via diet which is a main hurdle in research, newer ways walnuts per day. to enhance the level of Q in these area must be SOME GENETIC AND CELLULAR FACTORS THAT developed.

AFFECT AGING PROCESS ARE STATED BELOW Autophagy

The word derived from Greek word to eat oneself. Autophagosomes fuses with lysosome gives rise to autophagolysosomes in which cytoplasm degraded and the products again recycled and remain useful for synthesis of new compounds. Various studies in models like C. elegans, mice shown the effect of autophagy on aging process.

Theories Postulated To Demonstrate Age Reversing Phenomenon

The Acidification Theory of Aging The Autoimmune Theory The Caloric Restriction Theory The Cross-Linking Theory The Death Hormone Theory (DECO) The DNA and Genetic Theories The Errors and Repairs Theory The Free Radical Theory The Hayflick Limit Theory The Membrane Theory of Aging

Epigenetic changes
The role of DNA damage and maintaining chromatin is well known in aging related changes like
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The Mitochondrial Decline Theory The Neuroendocrine Theory The Redundant DNA Theory The Telomerase Theory of Aging The Thymic-Stimulating Theory The Wear and Tear Theory Out of these theories the most recent breakthrough has been achieved in The Telomerase Theory of Aging: Before moving further with the telomerase theory of aging let us understand structural and functional details of telomere. The telomere is a special functional complex at the end of linear eukaryotic chromosomes, consisting of tandem repeat DNA sequences and associated proteins. It is essential for maintaining the integrity and stability of linear eukaryotic genomes. Telomere length regulation and maintenance contribute to normal human cellular aging and human diseases. The synthesis of telomeres is What are telomeres? mainly achieved by the Who received the cellular reverse transcriptase telomere theory? telomerase, an RNAdependent DNA polymerase that adds telomeric DNA to telomeres. Expression of telomerase is usually required for cell immortalization and long-term tumor growth. In humans, telomerase activity is tightly regulated during development and oncogenesis. The modulation of telomerase activity may therefore have important implications in anti-aging and anticancer therapy.

aging in mice. The biological clock of these mice had been modified to make them age rapidly. This was done with genetic engineering which knocked out the gene that makes telomerase, the enzyme responsible for maintaining the telomeres. These genetically manipulated mice had short telomeres, and premature aging with atrophy (shrinkage) of the brain, spleen, loss of sense of smell, and loss of fertility with testicular atrophy. The next step of the experiment was to give back the missing gene for telomerase and see if that would reverse all these signs of aging in the mice. For this next step, the aged mice were treated with a drug (4-OHT), which served to turn on production of telomerase and lengthen the telomeres. This dramatically reversed the signs of aging with the aged mice surprisingly rejuvenated. Their shrunken brains, spleens and testes resumed normal size, and they regained their sense of smell. The aged infertile Nobel Prize for the males once again became fertile, and fathered large litters. Is this the next antiaging breakthrough? Can treatment to restore telomerase and telomere length potentially restore organ function and reverse degenerative disease in the elderly?

What is a Telomere?
Telomeres are the biological clock that control aging and cell replication. They are small strands of DNA code at the end of each chromosome. Each time the cell replicates itself, the telomere shortens a little bit and eventually, after about 50 replications, cell replication stops in a process known as cell senescence, or the Hayflick limit.

The Telomerese Theory of Aging

A new theory of aging that holds many promising possibilities for the field of anti-aging medicine is the telomerase theory of aging. This theory was born from the surge of technological breakthroughs in genetics and genetic engineering. First discovered by a group of scientists at the Geron Corporation in Menlo Park, California, telomeres are sequences of nucleic acids extending from the ends of chromosomes. Telomeres act to maintain the integrity of our chromosomes. Every time our cells divide telomeres are shortened, leading to cellular damage and cellular death associated with aging. Scientists discovered that the key element in rebuilding disappearing telomeres is the immortalizing enzyme telomerase, an enzyme found only in germ cells and cancer cells. Telomerase appears to repair and replace telomeres manipulating the clocking mechanism that controls the life span of dividing cells. Future development of telomerase inhibitor may be able to stop cancer cells from dividing and presumably may convert them back into normal cells.

Telomere function

Anti-Aging Breakthrough with Telomerase

A new study by Harvard professor Ronald A. De Pinho, published in Nature shows dramatic reversal of
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Nobel Prize for Telomere Research

develop safe products as nutritional supplements to activate telomerase and reverse aging. Dr. Andrews says Telomerase activation technology promises to be the most significant advance in human health since germ theory. Despite the monumental progress in aging research there has to be a unanimous vote on one specific theory of aging, Most of these theories have been disputed by scientists over and over again. Age-related changes do not occur uniformly in individuals; rather they are controlled jointly by genetic and environmental factors which further heighten the difficulty of finding a universal theory. What is universal is that we are all involved in a global-aging phenomenon. Through theoretical gerontology and antiaging medicine we may eventually discover there is no limit to human life span. How to Turn on Telomerase Activity Current Strategies and Issues Regarding Anti By now, it is should be obvious that activating Aging Drugs telomerase, protects the telomeres from shortening and Products that claim to cure or reverse aging mislead serves as an anti-aging treatment, slowing or reversing the public; presently there is no proven way to delay aging. On the contrary, knocking out or inhibiting the human aging process. One can delay some of the telomerase activity results in shortened telomeres with many effects of aging. For example, if one avoids acceleration of the aging process. unprotected exposure to the sun, one can delay skin Estrogen Activates Telomerase aging. Similarly, a balanced diet can lower the The major mechanism for control and activation of incidence of heart disease. Given the complexity of telomerase is the hTERT promoter gene which stands aging, however, delaying the onset of a single agefor the human Telomerase related disease cannot Reverse Transcriptase How can telomerace be activated? scientifically be considered (hTERT) gene. When the as equivalent to delaying the What are Estrogen blockers? hTERT gene is sequenced, aging process as a whole. and the code examined, one finds two estrogen Just because a given product or lifestyle delays the onset receptor elements in this gene. This explains why 17of a particular age-related change or pathology does beta estradiol activates telomerase. Simply put the fact not mean it delays aging, in the same way that that there are estrogen receptors in the TERT gene antibiotics used to treat opportunistic infections in means that estrogen activates telomerase. patients with AIDS, even if they preserve health, are Estrogen Blockers not targeting the ultimate cause of AIDS which is HIV. Estrogen blockers such as tomoxifen block these There are also ways of living longer. Following all that receptors and turn off telomerase. Androgens were also motherly advice like regular exercise and adequate found to turn on the hTERT gene and activate nutrition can make you live longer, and any therapy that telomerase, and as expected, androgen blocker drugs ameliorates mortality from a specific disease will increase inhibit telomerase. longevity. Still, living longer does not necessarily mean Bioidentical Hormones Levels Decline after Age 50 that the fundamental process of aging has been slowed down. Living a healthy life will lower your mortality Bioidentical hormones are the hormones normally across the entire lifespan, even if there is no impact on aging found in the human body. After age 50, hormone levels and age-related changes. For example, longevity decline in men and women, heralding the onset of increased roughly 50% in the past century and yet there degenerative changes also known as aging. It makes is no evidence people age slower; we live longer now sense to replenish these hormones to normal levels mostly because deaths caused by infectious diseases have which we now know activates telomere lengthening, gone down. This important distinction holds true for and reverses senescence. animal studies. Royal jelly and fish oil can significantly The Race for Natural Substances That Activate increase the average lifespan of mice, and yet that does Telomerase and Reverse Aging not mean that aging has been delayed by these treatments; Resveratrol, Silymarin and Gingko Biloba are all it means is that these nutrients are healthy. Therefore, natural substances found to activate telomerase with a great deal of care is necessary when interpreting lifepotential for anti-aging. Calvin Harley of Geron extension studies and there is a lot of room for controversy Corporation, and John Anderson and William H of what represents delayed aging. Andrews of Sierra Sciences are leading the race to Carol Greider and colleagues were awarded the 2009 Nobel Prize in Medicine for their discovery and work on telomerase, the enzyme that lengthens telomeres. In 1984, Greider discovered the enzyme telomerase and later she found that telomerase can prevent shortening of the telomeres, which prevents and reverse the aging process. Her findings were published in 1985 in the journal, Cell. Later, in 1997, Greider collaborated with Ronald A. De Pinho to produce a telomerase Knockout Mouse, a mouse genetically modified to have the telomerase enzyme removed, causing short telomeres and premature aging. This was the rapid aging mouse model used by De Pinho in his new study published in Nature.

So how can we determine whether a given cardiovascular disease, mental decline, poor immune intervention delayed aging? Based on the definition of response, and sense of poor health. Other controversial aging, a given intervention to be accepted as anti-aging anti aging practices involve BOTOX treatment. must demonstrate that the onset or pace of multiple Dynamic wrinkles result from overactive movements of age-related changes, including pathologies, is delayed. underlying muscles leading to skin creases; these are In addition, while accurately quantifying the rate of fairly easily corrected with botulinum toxin type A. aging is impossible, one method to estimate the rate of This has become the most common cosmetic procedure. aging is to calculate the rate at which mortality The US Food and Drug Administration has increases with age and so determining whether a given approved Clostridium botulinum toxin type A injections intervention delays this rate can also help determine for cosmetic treatment of glabellarrhytides. Two if the aging process was delayed . Any intervention that versions of botulinum toxin type A have been approved fails to meet these criteria cannot be considered as truly by the agency: onabotulinum toxin (Botox) and anti-aging, even if it extends average lifespan or delays abobotulinum toxin (Dysport). a given age-related change. This debate concerning Anti-aging physicians call this process of hormone what anti-aging means is the major source of confusion decline, somatopause concerning anti-aging (decrease in HGH), What is multi-hormone optimization? medicine and is often used andropause (decrease in sex by companies and even What is hormone modulation? hormones), adrenalpause scientists to mislead the (decrease in DHEA) and public. Certainly, some products pitched as anti-aging pinealpause (decrease in melatonin). These hormonal may be healthy and/or may soften the effects of aging. variations correlate with symptoms such as being over For example, a given anti-wrinkle cream may soften fat, decline in glucose tolerance, loss of muscle mass, one particular effect of aging (wrinkles) but it will not high cholesterol, and decreased cardiac endurance, all impact on any other aging sign. Importantly, an anti- of which are typically associated with aging. Antiwrinkle cream will not increase longevity much less aging physicians believe that these shifts can be delay the mortality acceleration with age and so cannot slowed or even reversed with strategic hormone be scientifically considered as anti-aging. replacement. Anti-aging hormone modulation is not to be As you might imagine, not all physicians agree with confused with the super-physiologic abuses of anabolic hormone modulation. Our current understanding of hormones by some bodybuilders and other athletes. anti-aging hormone replacement is very similar to Unmonitored hormone supplementation and treatment of menopause in the 1950s. At that time it experimentation is clearly dangerous. When it was was shown that giving estrogen to menopausal women revealed that Mark McGwire was taking the hormone reduced the incidence of osteoporosis and heart androsteindione, many aspiring athletes began taking disease, as well as ameliorating hot flashes, sweats andro. Later research determined this practice to be and other symptoms of menopause. However, long self-defeating and dangerous. Unscrupulous term consequences were not known. Many forwardsupplements manufacturers, physicians, drug thinking doctors used this therapy in increasing salesman and internet promoters have jumped on the numbers over time with good results. Forty years later, anti-aging hormone bandwagon, promoting their postmenopausal estrogen administration is now the modern-day snake oil to be consumed by the naive norm. Nevertheless, we must keep in mind that the consumer. risks of anti-aging hormone modulation are not fully Probably the most controversial anti-aging therapy understood, and shouldnt be underestimated. These is called multi-hormone optimization. This practice is hazards include increased growth of undiagnosed based on the Neuroendocrine theory of aging. This cancers, cardiovascular complications, liver damage, theory notes that when one is young hormone levels stroke and possibly other yet-to-be-discovered tend to be high and decline as one matures, usually complications. after age thirty. Hormones are vital for repairing and The anti-aging movement, while embracing regulating our bodily functions. This age-related sophisticated high-tech innovations, aligns itself decrease in the production of key hormones such as mostly with economical and pragmatic lifestyle DHEA, melatonin, testosterone, thyroid and human modifications. The effectiveness of proper diet, exercise growth hormone (HGH) is associated with a decline and social support cannot be overstated. Although we in the bodys ability to repair and regulate itself. In live in a youth-oriented culture that places a premium addition, catabolic hormones such as cortisol, insulin on beauty, fitness, pleasure-seeking indulgence and and estrogen (in men) increase as one age. Overall, sexuality, the anti-aging movement is about extending these multiple hormonal changes result in fat gain, loss the quality of life with a healthy recognition of our of muscle mass (sarcopenia), fatigue, insulin resistance, ultimate limitations. KK
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