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
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:
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
immune system. though none has been proven as anti-aging drugs. a Resveratrol. none has yet been proven to aging although they can slightly increase longevity. in part because of its “rejuvenate” mitochondria by optimizing metabolism negative side-effects. Resveratrol is a sirtuin stimulant in human cells. Succinctly. It does acetylcysteine. The many diets appear to increase with DHEA. therapy. • What is IGF-1? improving arterial elasticity. Other side-effects might include weight gain. 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. shown to retard or reverse the biological effects of many studies indicate that antioxidants do not slow ageing in animal models. in mice. lipoic acid. it however. like it can happen in arteries. Fortunately. and benefits to the skin. the cancer will spread faster. etc. might extend human life. Although HGH is not mutagenic. This hormone is generally used in conjunction Vitamin E. the latter hypothesized by diet and Caloric restriction. ALT-711 is one of the latest anti-aging compounds Insulin-like growth factor 1 (IGF-1) is another to receive worldwide attention. and E and co-enzyme Q10. • What is Anti-aging Medicine ameliorate aging’s effects. insulin. elderly by a variety of ways: Diets and supplements improved memory. contradictory. observed. against cancer has also been argued but some types of although few of these have been systematically tested cancer—namely prostate and breast cancer—actually for significant longevity effects. cells possess an array of defenses called Some supplements. there is little evidence any of Several drugs and food supplements have been these products actually work. The most serious side effect is or membrane potential. either in animal models or in cancer and take HGH. diabetes. Unfortunately. Other substances Antioxidants proposed to extend lifespan include oxytocin. One theory of aging is the free radical theory of human chorionic gonadotropin (hCG) and aging. lifespan of rats and mice. Common antioxidants include to do so in humans. probably cancer.similar class of compounds is aimed at quenching ROS patients in which they claim to feel younger after HGH treatment. 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. Since one major source of ROS is mitochondria. none of these products has been proven to makes cancer grow. C. 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. Protection diets or supplements—as a means to extend lifespan. To fight organisms such as nematodesand short-lived fish. While HGH was once hailed as a major production in mitochondria. Like GH. a chemical found in red grapes. 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 free radical theory of aging suggests that Finally. which means that if you have a have any effect on aging. including the minerals antioxidants many of which can be synthesized or seleniumor zinc have been reported to extend the extracted. generally in tablets. it only antioxidants but products that allegedly failed to live up to expectations. for women. there is probably little if nothing wrong with taking these products as serious side-effects have not been Anti Aging Medicine described. purified. ROS. Like for many other products. like many other anti-aging products. and then sold. These can include not breakthrough. do so in humans. humans. IGF-1’s product crosslink occur when glucose is attached to a levels decline with age and. mutations in mice 711 seems to be useful against heart disease by that lower IGF-1 seem to reducing pulse pressure and extend lifespan. such as Vitamin C. it releases reactive compounds called that appears to extend lifespan in simple model free radicals or reactive oxygen species (ROS). has
. when oxygen is used to make energy erythropoietin (EPO). Q10. and significant toxic effects were vitamins A. Carnosine and Nwith others in hormone replacement therapy. In mice. 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. Much life extension research focuses on nutrition— sexual appetite. For this. muscle mass. ALT1 appear to correlate with longevity. for instance. Minor side effects such promoted by anti-aging advocates are often as acne have also been reported. some to be associated with aging and life-extension. estrogen is a popular anti-aging antioxidant supplements. However. high ALT-711 blood pressure. low levels of IGFprotein.
to enhance the level of Q in these area must be SOME GENETIC AND CELLULAR FACTORS THAT developed. 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. researchers at oxidative stress due to free the Salk Institute for • What is Co-enzime Q? radicals. Human klotho Biological Studies. Deficiency of Q level associated with Also in 2009. As rats could be improved by adding walnuts to their diet. Professor conditions. protein Small doses of heavy water increase fruit-fly turn over regulation. 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. Deficiency of gene causes several aging related links eating fewer calories with living longer. stress and immune lifespan by 30%. • What is the role of Kiotho gene in endothetical? well as by decreasing In 2007. antioxidant part old mice by up to 38%. degenerations. space determines the chance of survival and In 2002.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. Klotho gene pha-4 regulates the longevity response to calorie found useful in regulating endothelial dysfunction. DNA damage repair and many more. restriction. identified gene present mainly in a critical gene in nematode worms that specifically kidney. newer ways walnuts per day. 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. a team led by Professor Bruce Ames at UC maintenance. elegans. detoxification. 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. in various important systems in cell like respiratory was found to extend the life expectancy of 20-monthtransport chain (in mitochondria). if any contraction in this space leads to Berkeley discovered that feeding aged rats a aging and related diseases. on the other hand. It does not extend the lifespan of healthy sensitive towards cellular decline. mice shown the effect of autophagy on aging process.been shown to extend the lifespan of yeast by 60%. but large doses are toxic to complex response. over-expression can Andrew Dillin and colleagues showed that the increase the life span in mammals by 20-30%. senescence. a drug called rapamycin. In the same year Dr Howard Chang of Klotho is emerging as very important anti-aging gene. It works by enabling the gene SRT-1 which Various genes whose products and interactions mimics the effect of calorie restriction. This organisms. which in some creates homeodynamic space based upon the different animals has been shown to lengthen lifespan. It is also one of essential factor 1970s in the soil of Easter Island in the South Pacific. enzymes. and genetic worms and flies by 30% and one species of fish by abnormalities. 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. The role of coenzyme Q (Q) in cellular In 2009.
AFFECT AGING PROCESS ARE STATED BELOW Autophagy
The word derived from Greek word to eat oneself. repair mechanisms like free radical scavenging. mice but delays the onset of age-related disease and Hormesis infirmity. These changes make cell more and more almost 60%. discovered in the respiration is crucial. improper cell functioning.
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
The role of DNA damage and maintaining chromatin is well known in aging related changes like
It is essential for maintaining the integrity and stability of linear eukaryotic genomes. Expression of telomerase is usually required for cell immortalization and long-term tumor growth. Future development of telomerase inhibitor may be able to stop cancer cells from dividing and presumably may convert them back into normal cells. 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. spleens and testes resumed normal size. the aged mice were treated with a drug (4-OHT). telomeres are sequences of nucleic acids extending from the ends of chromosomes. the telomere shortens a little bit and eventually. Telomerase appears to repair and replace telomeres manipulating the “clocking” mechanism that controls the life span of dividing cells. The modulation of telomerase activity may therefore have important implications in anti-aging and anticancer therapy. These genetically manipulated mice had short telomeres. and premature aging with atrophy (shrinkage) of the brain. This dramatically reversed the signs of aging with the aged mice surprisingly rejuvenated. or the Hayflick limit. The “biological clock” of these mice had been modified to make them age rapidly. and loss of fertility with testicular atrophy. The telomere is a special functional complex at the end of linear eukaryotic chromosomes. Each time the cell replicates itself. and fathered large litters. published in Nature shows dramatic reversal of
. For this next step. and they regained their sense of smell. consisting of tandem repeat DNA sequences and associated proteins. Every time our cells divide telomeres are shortened. the enzyme responsible for maintaining the telomeres. an RNAdependent DNA polymerase that adds telomeric DNA to telomeres.
• • • • • •
aging in mice. after about 50 replications. spleen.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.
Anti-Aging Breakthrough with Telomerase
A new study by Harvard professor Ronald A. 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. Telomere length regulation and maintenance contribute to normal human cellular aging and human diseases. In humans. Telomeres act to maintain the integrity of our chromosomes. telomerase activity is tightly regulated during development and oncogenesis. This theory was born from the surge of technological breakthroughs in genetics and genetic engineering. leading to cellular damage and cellular death associated with aging. which served to “turn on” production of telomerase and lengthen the telomeres. an enzyme found only in germ cells and cancer cells. cell replication stops in a process known as “cell senescence”. Scientists discovered that the key element in rebuilding disappearing telomeres is the “immortalizing” enzyme telomerase. loss of sense of smell. The aged infertile Nobel Prize for the males once again became fertile. De Pinho. The synthesis of telomeres is • What are telomeres? mainly achieved by the • Who received the cellular reverse transcriptase telomere theory? telomerase. They are small strands of DNA code at the end of each chromosome. California. First discovered by a group of scientists at the Geron Corporation in Menlo Park.
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. Their shrunken brains. This was done with genetic engineering which “knocked out” the gene that makes telomerase.
and John Anderson and William H of what represents delayed aging. Silymarin and Gingko Biloba are all it means is that these nutrients are healthy. Therefore. Given the complexity of telomerase is the hTERT promoter gene which stands 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.Nobel Prize for Telomere Research
develop safe products as nutritional supplements to activate telomerase and reverse aging. patients with AIDS. one finds two estrogen Just because a given product or lifestyle delays the onset receptor elements in this gene. How to Turn on Telomerase Activity Current Strategies and Issues Regarding Anti By now. longevity decline in men and women. even if they preserve health. and the code examined. and any therapy that telomerase. What is universal is that we are all involved in a global-aging phenomenon. Simply put the fact not mean it delays aging. longevity. 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. Andrews says “Telomerase activation technology promises to be the most significant advance in human health since germ theory. Still. in 1997. Most of these theories have been disputed by scientists over and over again. a mouse genetically modified to have the telomerase enzyme removed. For example. one can delay skin Estrogen Activates Telomerase aging. Her findings were published in 1985 in the journal. aging process as a whole.” Despite the monumental progress in aging research there has to be a unanimous vote on one specific theory of aging. Greider discovered the enzyme telomerase and later she found that telomerase can prevent shortening of the telomeres. De Pinho to produce a telomerase “Knockout Mouse”. hormone levels and age-related changes. if one avoids acceleration of the aging process. knocking out or inhibiting the human aging process. which prevents and reverse the aging process. 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. Similarly. Age-related changes do not occur uniformly in individuals. living longer does not necessarily mean Bioidentical Hormones Levels Decline after Age 50 that the fundamental process of aging has been slowed down. This important distinction holds true for and reverses senescence. Estrogen blockers such as tomoxifen block these There are also ways of living longer.
. presently there is no proven way to delay aging. Resveratrol. heralding the onset of increased roughly 50% in the past century and yet there degenerative changes also known as aging. natural substances found to activate telomerase with a great deal of care is necessary when interpreting lifepotential for anti-aging. This was the rapid aging mouse model used by De Pinho in his new study published in Nature. When the as equivalent to delaying the • What are Estrogen blockers? hTERT gene is sequenced. It makes is no evidence people age slower. animal studies. Greider collaborated with Ronald A. For example. are Estrogen Blockers not targeting the ultimate cause of AIDS which is HIV. Through theoretical gerontology and antiaging medicine we may eventually discover there is no limit to human life span. and yet that does Telomerase and Reverse Aging not mean that aging has been delayed by these treatments. causing short telomeres and premature aging. In 1984. After age 50. Following all that receptors and turn off telomerase. Royal jelly and fish oil can significantly The Race for Natural Substances That Activate increase the average lifespan of mice. protects the telomeres from shortening and Products that claim to cure or reverse aging mislead serves as an anti-aging treatment. This explains why 17of a particular age-related change or pathology does beta estradiol activates telomerase. a balanced diet can lower the The major mechanism for control and activation of incidence of heart disease. rather they are controlled jointly by genetic and environmental factors which further heighten the difficulty of finding a universal theory. On the contrary. unprotected exposure to the sun. slowing or reversing the public. Calvin Harley of Geron extension studies and there is a lot of room for controversy Corporation. Dr. Living a healthy life will lower your mortality Bioidentical hormones are the hormones normally across the entire lifespan. 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. 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. the enzyme that lengthens telomeres. however. androgen blocker drugs ameliorates mortality from a specific disease will increase inhibit telomerase. and as expected. Later. Cell. One can delay some of the telomerase activity results in shortened telomeres with many effects of aging. even if there is no impact on aging found in the human body. it is should be obvious that activating Aging Drugs telomerase. gone down.
as well as ameliorating hot flashes. and shouldn’t be underestimated. KK
. while accurately quantifying the rate of fairly easily corrected with botulinum toxin type A. sweats andro. These hormonal may be healthy and/or may soften the effects of aging. This cancers. However. we must keep in mind that the consumer. 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. aging is impossible. some products pitched as anti-aging pinealpause (decrease in melatonin). Later research determined this practice to be and other symptoms of menopause. risks of anti-aging hormone modulation are not fully Probably the most controversial anti-aging therapy understood. Two if the aging process was delayed . usually complications. all impact on any other aging sign. In live in a youth-oriented culture that places a premium addition. not all physicians agree with confused with the super-physiologic abuses of anabolic hormone modulation. including pathologies. anti-aging hormone replacement is very similar to Unmonitored hormone supplementation and treatment of menopause in the 1950s. Overall. and sense of poor health. fatigue. loss of muscle mass. decline in glucose tolerance. a given anti-wrinkle cream may soften fat. Although we in the body’s ability to repair and regulate itself. replacement. Other controversial aging. exercise growth hormone (HGH) is associated with a decline and social support cannot be overstated. fitness. cardiovascular complications. insulin on beauty. loss the quality of life with a healthy recognition of our of muscle mass (sarcopenia). adrenalpause scientists to mislead the (decrease in DHEA) and public. mental decline. Certainly. This practice is hazards include increased growth of undiagnosed based on the Neuroendocrine theory of aging. the anti-aging movement is about extending these multiple hormonal changes result in fat gain. one particular effect of aging (wrinkles) but it will not high cholesterol.of which are typically associated with aging. physicians. ultimate limitations. At that time it experimentation is clearly dangerous. Anti-aging hormone modulation is not to be As you might imagine. one method to estimate the rate of This has become the most common cosmetic procedure. Our current understanding of hormones by some bodybuilders and other athletes. “anti-aging hormone” bandwagon. 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. 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. aligns itself decrease in the production of key hormones such as mostly with economical and pragmatic lifestyle DHEA. The effectiveness of proper diet. drug thinking doctors used this therapy in increasing salesman and internet promoters have jumped on the numbers over time with good results. thyroid and human modifications. sexuality. even if it extends average lifespan or delays abobotulinum toxin (Dysport). This age-related sophisticated high-tech innovations. insulin resistance. 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. and decreased cardiac endurance. poor immune intervention delayed aging? Based on the definition of response. Importantly. 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. • What is multi-hormone optimization? medicine and is often used andropause (decrease in sex by companies and even • What is hormone modulation? hormones). long self-defeating and dangerous. somatopause concerning anti-aging (decrease in HGH). is delayed. underlying muscles leading to skin creases. Unscrupulous term consequences were not known. Forty years later. while embracing regulating our bodily functions. pleasure-seeking indulgence and and estrogen (in men) increase as one age. a given intervention to be accepted as anti-aging anti aging practices involve BOTOX treatment. many aspiring athletes began taking disease. 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. These is called multi-hormone optimization. Hormones are vital for repairing and The anti-aging movement.So how can we determine whether a given cardiovascular disease. after age thirty. an anti. promoting their postmenopausal estrogen administration is now the modern-day snake oil to be consumed by the naive norm. melatonin. must demonstrate that the onset or pace of multiple Dynamic wrinkles result from overactive movements of age-related changes. these are In addition. variations correlate with symptoms such as being over For example. catabolic hormones such as cortisol. Nevertheless. testosterone. Many forwardsupplements manufacturers. liver damage.