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Aging is an accumulation of damage to Macromolecule s, Cells , Tissues and Organs . The Maximum Lifespan of a Human is about 120 years, whereas the maximum lifespan of a Mouse is about 3 years. Genetic differences between humans and mice that can account for these different aging rates include efficiency of DNA Repair , types and quantities of Antioxidant Enzyme s, different rates of Free Radical production, etc. (See Senescence for more detail on aging theories.) Extension of maximum lifespan can be achieved by reducing the rate of aging damage, by periodic replacement of damaged tissues or by Molecular repair ( Rejuvenation ) of damaged tissues. Researchers of life extension are a subclass of Biogerontologists known as "biomedical Gerontologists ". They seek to understand the nature of aging and they develop treatments to reverse aging processes or to at least slow them down, for the improvement of health and the maintenance of youthful vigor at every stage of life. (Biomedical gerontologists are distinguished from Biogerontologists in that the latter only take an academic interest in the Biological Mechanisms Of Aging , without seeking a "cure".) Those who take advantage of life extension findings and seek to apply them upon themselves are called "'''life extensionists'''". The primary life extension strategy currently is to apply available anti-aging methods in the hope of living long enough to benefit from a complete cure to aging once it is developed, which given the rapidly advancing state of biogenetic and general medical technology, could conceivably occur within the lifetimes of people living today. Many biomedical gerontologists and life extensionists believe that future breakthroughs in tissue Rejuvenation with Stem Cell s, Organs replacement (with artificial Organs or Xenotransplantation s) and Molecular repair will eliminate all aging and disease as well as allow for complete rejuvenation to a youthful condition. Whether such breakthroughs can occur within the next few decades is doubtful. Many life extensionists make Cryonics arrangements, ie, arrange to be Cryopreserve d, upon legal death so that they can await the time when future Medicine can eliminate Disease , Rejuvenate to a lasting youthful condition and repair damage caused by the Cryopreservation process. Whether the maximum human lifespan should be extended is the subject of much political and scientific controversy. But the life extension movement, which began in the early 1980s, continues to grow in popularity and momentum. STRATEGIES OF LIFE EXTENSION Anti-Aging Medicine Much of anti-aging medicine has been concerned with the use of nutritional supplements to extend lifespan. The idea that Antioxidant Supplements , such as Vitamin E , Lipoic Acid and N-acetylcysteine , might extend human life stems from the Free Radical Theory of Aging . Diabetes resembles accelerated Aging and is associated with cross-linking of Protein s by Sugar s, more specifically Monosaccharide s. Some believe that anti- Glycating supplements (supplements that reduce the protein cross-linking by monosaccharides), such as Carnosine , pyridoxamine, benfotiamin and Lysine , might reduce aging. Restoring youthful levels of Growth Hormone , Melatonin or DHEA (all of which decline with age) has also been tried as means of reducing aging. Although some supplements have been shown to be of benefit against some aging-related disease conditions, or have extended average lifespan, only calorie restriction has been shown to extend maximum lifespan in any species. Calorie Restriction See Also: Calorie restriction Calorie restriction (CR) with adequate nutrition has been shown to extend the maximum lifespan of almost every species on which it has been tested, including rats, yeast, fruit flies, and nematodes. In rodents, a roughly 50% maximum lifespan extension is seen with a roughly 50% restriction of calories from what would be consumed by freely-feeding animals. Experiments are in progress with primates to test whether calorie restriction can extend the lifespan of long-lived species. Some people believe that these experiments will be successful, and that the results will similarly hold true for humans. A group called the Calorie Restriction Society was formed with the help of Roy Walford in the mid-1990s. These people may have the willpower and determination to restrict their caloric intake in the hope of extending their lives, but they are very few in number. They communicate by e-mail and have been flown to Washington University in St. Louis to be studied by Dr. John Holloszy. There has been some Criticism of Calorie restriction. Chemical and genetic interventions in animal models Numerous animal experiments have shown that Growth Hormone generally acts to shorten lifespan; Knockout Mice lacking the Receptor for growth hormone live especially long. Resveratrol is a substance that has been shown to extend the lifespan of yeast, fruit flies and certain fishes. Experiments in mammals are currently underway. The manner by which resveratrol achieves this effect remains unknown, although it has been conjectured that it is involved in the mechanism that underlies the lifespan enhancing effects of calorie restriction. Likewise, the Sir2 class of genes is conjectured to be involved in the calorie restriction mechanism; yeast genetically engineered to overexpress Sir2 live longer. Large availability of Insulin generally leads to shorter lifespan. Mice genetically engineered to lack an insulin receptor in fat tissue live longer. Mice with an overexpression of the Klotho Gene , which limits insulin sensitivity, also show an extended lifespan. SENS (Strategies for Engineered Negligible Senescence) See Also: Engineered negligible senescence Dr. Aubrey De Grey has suggested that it will someday be possible for humans to live thousands of years in a youthful condition. He calls his project to reverse the damage we call ''aging'' ''' SENS (Strategies For Engineered Negligible Senescence) '''. He has proposed seven strategies for the "seven deadly sins": # Cell loss can be repaired (reversed) just by suitable Exercise in the case of Muscle . For other tissues it needs various Growth Factor s to stimulate Cell Division , or in some cases it needs Stem Cells . # Senescent Cells , can be removed by activating the Immune System against them. Or they can be destroyed by Gene Therapy to introduce "suicide Gene s" that only kill senescent cells. # Protein Cross-linking can largely be reversed by Drugs that break the links. But to break some of the cross-links we may need to develop enzymatic methods. # Extracellular garbage (like Amyloid ) can be eliminated by Vaccination that gets Immune cells to "eat" the garbage. # For intracellular junk we need to introduce new Enzyme s, possibly enzymes from soil Bacteria , that can degrade the junk ( Lipofuscin ) that our own natural enzymes cannot degrade. # For Mitochondrial mutations the plan is not to repair them but to prevent harm from the mutations by putting suitably modified copies of the mitochondrial genes into the Cell Nucleus by gene therapy. The Mitochondrial DNA experiences a high degree of Mutagenic damage because most Free Radicals are generated in the Mitochondria and because the DNA repair mechanisms of mitochondrial DNA are significantly inferior to those of nuclear DNA. A copy of the mitochondrial DNA located in the Nucleus will be better protected from free radicals, and there will be better DNA Repair when damage occurs. All mitochondrial Protein s would then be imported into the mitochondria. # For Cancer (the most lethal consequence of mutations) the strategy is to use Gene Therapy to delete the Gene s for Telomerase and to eliminate telomerase-independent mechanisms of turning normal cells into "immortal" cancer cells. To compensate for the loss of telomerase in Stem Cells we would introduce new stem cells every decade or so. Dr. de Grey has created the Methuselah Mouse Prize , which awards money to researchers who can extend the lifespan of Mice or Rejuvenate mice. Cryonics See Also: Cryonics Cryonics is inspired by the fact that life extension technologies may eventually allow people to live thousands of years of youthful life. But these technologies may not be available for another 50 years, if ever. There is a danger that anyone, including young people, may die before the new medicine becomes available. Cryopreservation shortly after legal death may provide an " Ambulance " into the future. The basis of cryonics is that at Cryogenic temperatures there will be no alteration in biological tissue for thousands of years, which allows plenty of time for future medicine to achieve the required capabilities. For those in cryonics, future medicine will not only be able to cure all disease and rejuvenate everyone to a youthful condition, but it will be able to repair any damage that is caused by the Cryopreservation process. Molecular repair technology ( Nanotechnology and Nanomedicine ) is expected to be able to achieve these results. But to be safe, and to minimize damage, efforts have been made to eliminate all freezing damage through Vitrification and to minimize Ischemic damage through rapid cooling and Cardio - Pulmonary support immediately following pronouncement of death. Cryonics is not Freezing of humans or pets. Ice is very damaging to body Tissues , so all cryonics organizations use Cryoprotectant s to prevent Ice formation, ie, anti-freeze substances that can reduce or prevent ice formation. Formerly cryonics organizations used Glycerol as their cryoprotectant, which resulted in about 80% ice elimination ( Vitrification ) and about 20% freezing. Cryonicists believed that damage that was being caused by Disease , by Aging and by the freezing would someday be repaired by Nanotechnology . With Vitrification the burden on future technology has been greatly reduced. With Cells and Tissues mainly preserved by cooling, future technology should be able to repair damage resulting if the cooling process is not too delayed. Since the 1990s Vitrification solutions have been developed that have virtually eliminated ice formation (reduced to less than 0.2%). In fact, it was announced in July 2005 that one such solution had been used to vitify Rabbit Kidney at -135°C, and was later Transplanted into a rabbit with full Viability . Stoppage of Heartbeat and Breathing , the usual criteria for legal Death , do not correspond to the death of Cells and Tissues of the body. The Cells and Tissues are still very much alive when death is pronounced. Even at room Temperature Cells and Tissues take hours to die, and days to Decompose . Although Neurological damage is the usual consequence of cessation of heartbeat for more than 4-6 minutes, the irreversible Neurodegenerative processes do not manifest for hours. Rapid cooling and Cardio - Pulmonary support applied immediately after pronouncement of death can preserve Cells and Tissues for long-term preservation at Cryogenic Temperature s. People, especially children, have survived up to an hour without heartbeat after having fallen into ice water. Cryonics "standby teams" wait by the bedside of cryonics patients to apply cooling and Cardio - Pulmonary support as soon as possible after declaration of death. Cryonicists do not believe that legal death is real death (irreversible destruction of the Anatomical basis of Mind ) any more than conventional Medicine now accepts that cessation of heartbeat is "real death", when the heart can be restarted with a Defibrillator . Mind Uploading Mind uploading is the Transfer of the human Mind / Consciousness to a more durable material vessel (stereotypically but not necessarily a Silicon Computer ). The concept is based on Materialism , the Philosophy Of Mind that argues that the human spirit is entirely composed of a very complex system of physical and chemical interactions. With computer power increasing exponentially, and technology in the pipeline to keep up the trend, Futurist Ray Kurzweil predicts that computer hardware will be powerful enough to run a functional model of the human mind by the 2020s. Several developing technologies promise to allow the complete mapping of human brains on a similar timescale. Uploading the human mind to a computer would potentially greatly extend human lifespan due to the ability to construct highly durable computer hardware and due to the potential to copy or transfer the mind to multiple computers. HISTORY OF LIFE EXTENSION AND THE LIFE EXTENSION MOVEMENT In 1970, the American Aging Association was formed under the impetus of Denham Harman originator of the Free Radical Theory of Aging . Harman wanted an organization of Biogerontologists that was devoted to research and to the sharing of information among scientists interested in extending human lifespan. Although the human desire to extend life can be traced at least to the Epic Of Gilgamesh , the 1982 bestselling book ''Life Extension'' (ISBN 044651229X) by Durk Pearson and Sandy Shaw popularized the phrase. The book deals largely with Antioxidant Supplements , and is dedicated foremost to Dr. Denham Harman. The 1980 book ''The Life Extension Revolution'' (ISBN 0688035809) by Saul Kent did not sell so well. But Mr. Kent appeared on the ''Merv Griffin Show'' with Pearson and Shaw, and was able to use the flood of letters to create the Nutraceutical firm called the Life Extension Foundation , which is non-profit. The Life Extension Foundation has grown to produce a magazine which has a large circulation. The group has a track record which includes promoting the benefits of many health supplements such as S-adenosyl Methionine and Melatonin many years before the medical field accepted the benefits of those substances. Money generated by the Life Extension Foundation allowed Saul Kent to finance the Alcor Life Extension Foundation , the largest Cryonics organization. The cryonics movement had been launched in 1962 by Robert Ettinger 's book, ''The Prospect of Immortality''. In the 1960s, Saul Kent had been a co-founder of the Cryonics Society of New York. Alcor gained national prominence when the baseball star Ted Williams was cryonically preserved by Alcor in 2002 and a family dispute arose as to whether Ted had really wanted to be Cryopreserved . In 1983, Dr. Roy Walford , a life-extensionist Gerontologist published a popular book called ''Maximum Lifespan''. Later, Dr. Walford and his student Dr. Richard Weindruch summarized years of their research into the ability of Calorie Restriction to extend the lifespan of Rodent s in their 1988 scholarly work ''The Retardation of Aging and Disease by Dietary Restriction'' (ISBN 0398054967). It had been known since the work of Clive McCay in the 1930s that calorie restriction can extend the maximum lifespan of rodents. But it was the work of Walford and Weindruch that gave detailed scientific grounding to that knowledge. Walford's personal interest in life extension motivated his scientific work and he practised calorie restriction himself. For years the FDA was in contention with the Life Extension Foundation, including through seizure of merchandise and court action. The FDA did not regard aging as a disease or life extension as a valid treatment category. In 1991 Saul Kent and Bill Faloon, the principals of the Foundation were jailed and told by the FDA that they would become the target of criminal indictments that would "destroy their lives forever" and were advised to plead guilty of crimes against the state. Against legal advice, Kent and Faloon fought the FDA in court and filed countercharges concerning their mistreatment. In 1995 the FDA informed Kent and Faloon that, in exchange for a guilty plea, they would not have to go to prison and could continue doing business on a more limited basis. Instead of pleading guilty, Kent and Faloon filed a new battery of legal motions, escalated their counterattack against the FDA and began extensive preparations for their trial. In November 1995, the FDA dropped all charges except the charge of "obstruction of justice" against Saul Kent. In February 1996, this charge was also dropped. In 1993 the American Academy of Anti-Aging Medicine (A4M) was formed to create an anti-aging medical specialty distinct from Geriatrics , and to hold conferences for physicians interested in this field. An important recent development in life extension has been the work of Biogerontologist Aubrey De Grey of Cambridge University . Dr. de Grey proposes that damage to Macromolecule s, Cell s, Tissue s and Organ s can be repaired by advanced Biotechnology . SCIENTIFIC CONTROVERSY ABOUT LIFE EXTENSION Anti-Aging Medicine Although Alex Comfort and Bernard Strehler have been retrospectively claimed as anti-aging Gerontologists , other Biogerontologists vehemently deny that aging is a disease. Possibly the most prominent biogerontologist making this denial is Leonard Hayflick , who determined that Fibroblast s are limited to around 50 cell divisions. Hayflick reasons that aging is an unavoidable consequence of Entropy . Dr. Denham Harman spent years experimenting with Antioxidant s, and was able to establish only that they can extend mean lifespan; he was unable to demonstrate an effect on maximum lifespan. In response to what they saw as unscrupulous profiteering by those engaged in the selling of Supplements and the practice of anti-aging medicine, a group of prominent Biogerontologists began a "war" on anti-aging medicine in general and the A4M in particular. Jay Olshansky , Leonard Hayflick , and Bruce Carnes wrote a position paper against anti-aging medicine (PMID 12145354). Calorie Restriction Despite the results on Yeast , Fruit Flies and Nematodes , criticisms have been raised that the results of calorie restriction experiments on laboratory rats are not generalisable because years of Inbreeding have made these animals different from those found in the wild. Even if it is conceded that the rat work may be generalisable to some extent, some argue that the results are applicable only to short-lived species that have evolved to respond to feast and famine with alterations in longevity. Proving that the results are generalisable in a way that encourages hope of extended life for human beings is difficult, since experiments with long-lived species necessarily take a very long time to perform. Scientists have varying theories on why calorie restriction experiments would increase the life spans of the animals who have been tested with it besides the calories being reduced. These include the Habitat , the Genetic line of the test subjects, and the Nutritional content of the animal's diets, and the frequencies of feeding. Some critics observe that the test animals are not exposed to the same stresses that humans are in everyday life in modern environments, which may give humans a greater need for the calories. A better explanation of the controversies is found on the Calorie Restriction wiki. SENS (Strategies for Engineered Negligible Senescence) The based on pure speculation, rather than on robust science. Aubrey De Grey has been criticized on the ground that he is a theoretician who does no empirical work himself. Yet Dr. de Grey collaborates extensively with experimental scientists, publishes several peer-reviewed scientific papers per year, organizes scientific conferences, and is editor-in-chief of the peer-reviewed journal ''Rejuvenation Research''. Detailed and concrete criticism of SENS Is Still Lacking . Aubrey de Grey's claim that the only significant effect of other than Mutation ( Cancer ), may be small in the young, it increases greatly with age. Moving mtDNA into the Nucleus would not be as beneficial as he presumes if nDNA is subject to such a decline in DNA Repair with age. A comparison of the Heart Mitochondria in Rat s (4-year lifespan) and Pigeon s (35-year lifespan) showed that Pigeon Mitochondria leak fewer Free Radicals than rat mitochondria, despite the fact that both Animal s have similar Metabolic rate and Cardiac Output . Pigeon heart Mitochondria ( Mammal s showed a direct correlation between Maximum Lifespan and Oxidative damage to mtDNA in Heart & Brain . There was a 4-fold difference in levels of oxidative damage and a 13-fold difference in Longevity , supportive of the idea that mtDNA Oxidative damage is not the only cause of Aging FASEB JOURNAL; Barja,G; 14(2):312-318 (2000) . The segmental both in the nucleus and in the s to our cells. Thus, improved DNA Repair and reduced Free Radical production (by Complex I proteins taken from Bird s) may be much more cost effective strategies than SENS for reducing aging-damage, extending Maximum Lifespan and preventing Cancer . Cryonics |
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