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Life extension, also known as anti-aging medicine, 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, and "life extensionists" or "longevists" (who wish to achieve longer lives for themselves), believe that future breakthroughs in tissue rejuvenation with stem cells, molecular repair, and organ replacement (such as with artificial organs or xenotransplantations) will eventually enable humans to have indefinite lifespans through complete rejuvenation to a youthful condition.

The sale of putative anti-aging products such as nutrition, physical fitness, skin care, hormone replacements, vitamins, supplements and herbs has become a lucrative industry, with the US market generating about $50 billion of revenue each year.^[1] Medical experts state that the use of such products has not been shown to affect the aging process, and many claims of anti-aging medicine advocates have been roundly criticized by medical experts, including the American Medical Association.^[1][2][3][4] Bioethicists question whether and how the human lifespan should be extended.

[edit] Aging

Aging is an accumulation of damage to macromolecules, cells, tissues and organs. The maximum life span for humans 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 afflictions such as cancer or cardiovascular disease play larger roles. Extension of average lifespan can 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 probably by certain 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.

[edit] Current anti-aging strategies and issues

[edit] Diets and supplements

Much of life extension has been concerned with the use of nutrition, in the form of diets or supplements, to extend lifespan. The many diets promoted by anti-aging advocates are often contradictory. Two diets with different approaches and some support from scientific research are the Paleolithic diet and Caloric restriction.^[5][6][7][8]

The restriction of energy intake, or calories, in an otherwise healthy diet (a practice generally called Calorie restriction or simply CR) has been shown to extend the maximum life span of laboratory organisms from several species, 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.^{[citation needed]} The results of calorie restriction experiments on laboratory rats may not be generalizable because years of inbreeding have made these animals different from those found in the wild, and because these results are applicable specifically to short-lived species that have evolved to respond to feast and famine with alterations in longevity.^{[citation needed]} Proving that calorie restriction could extend human life is difficult because experiments with long-lived species necessarily take a long time to perform. Scientists propose that the results of calorie restriction experiments on animals also depend on the habitat, genetics, other aspects of nutrition and frequencies of feeding.

The idea that antioxidant supplements, such as Vitamin C, Vitamin E, lipoic acid and N-acetylcysteine, might extend human life stems from the free radical theory of aging. Other substances proposed to extend lifespan include oxytocin, insulin, human chorionic gonadotropin (hCG) and erythropoietin (EPO). Resveratrol is a sirtuin stimulant that appears to extend lifespan in simple model organisms such as nematodes^[9] and short-lived fish.^[10]

Some supplements, including the minerals selenium^[11] or zinc^[12][13] have been reported to extend the lifespan of rats and mice, though none has been proven to do so in humans, and significant toxic effects were observed. Metformin^[14] may also extend life span in mice.

[edit] Cosmetics

Cosmetic interventions such as skin treatments (e.g., skin resurfacing, Botox treatments, Argireline products) and plastic surgery are widely used to mask the effects of aging, although they do not actually affect lifespan.

[edit] Hormone treatments

The anti-aging industry offers several hormone therapies. Some of these products have been criticized, for example by the American Medical Association, for possible dangers to the patient and a lack of proven effect.^[1]

The evidence for use of growth hormone is mixed and based on animal studies. An early study suggested that supplementation of mice with growth hormone increased average life expectancy.^[15] Additional animal experiments have suggested that growth hormone may generally act to shorten maximum lifespan; knockout mice lacking the receptor for growth hormone live especially long.^[16] Furthermore, mouse models lacking the insulin-like growth factor also live especially long and have low levels of growth hormone.^[16]

The synthetic estrogen Premarin (made from mare’s urine), has been proposed to reduce the impact of menopause. In 1991, the Women’s Health Initiative studied 161,808 postmenopausal women with randomized trials of hormone supplements or placebo. It discontinued the study in 2002 because it concluded that, on the whole, the supplements were doing more harm than good (primarily due to an increased risk of breast cancer). Testosterone supplements in the form of creams or patches have been proposed for men. Regular Human Growth Hormone (HGH) injections cost about $10–12,000 a year. On the internet, many websites promote less expensive secretagogues that claim to prompt the body to produce HGH. There is little independent research on HGH secretagogues.^{[citation needed]}

[edit] Scientific controversy regarding anti-aging nutritional supplementation and medicine

Leonard Hayflick, who determined that fibroblasts are limited to around 50 cell divisions, disputes the claim that aging is a disease. Hayflick reasons that aging is an unavoidable consequence of entropy. Hayflick and fellow biogerontologists Jay Olshansky and Bruce Carnes have strongly criticized the anti-aging industry in response to what they see as unscrupulous profiteering from the sale of unproven anti-aging supplements.^[3]

[edit] Ethics and politics of anti-aging nutritional supplementation and medicine

Politics relevant to the substances of life extension pertain mostly to communications and availability. In the United States, the claims which can be made on food and drug product labels are strictly regulated. Meanwhile, freedom of speech guaranteed by the First Amendment currently only protects the right of third-party publishers to print books, newsletters, websites, etc. on every aspect of these substances, including opinions, speculations, etc. Many manufacturers and suppliers also provide publications, but because they are also marketing the substances, they are subject to the monitoring and enforcement efforts of the Federal Trade Commission (FTC) which has jurisdiction over false claims made by marketers in public media. What constitutes the difference between truthful and false claims is hotly debated and is a central controversy in this arena.^{[citation needed]}

[edit] Proposed strategies of life extension

Raymond Kurzweil, a futurist and transhumanist, believes that advanced medical nanorobotics could completely cure aging by 2030.^[17] According to Kurzweil, applying successive anti-aging methods as they become available could allow individuals to live long enough to benefit from a complete cure to aging once it is developed.^{[citation needed]}

[edit] Cloning and body part replacement

Some life extensionists suggest that therapeutic cloning and stem cell research could one day provide a way to generate cells, body parts, or even entire bodies (generally referred to as reproductive cloning) that would be genetically identical to a prospective patient. In one experiment, a functioning dog's bladder was grown and proved to be viable after implantation.^{[citation needed]} Recently, the US Department of Defense initiated a program to research the possibility of growing human body parts on mice.^[18] Complex biological structures, such as mammalian joints and limbs, have not yet been made. In one popular scenario, an individual's brain is transplanted from his or her aging body into a new, youthful body cloned from his or her own tissues. Dog and primate brain transplantation experiments were conducted in the mid-20th century but failed due to rejection and the inability to restore nerve connections. Proponents of body part replacement and cloning contend that the required biotechnologies are likely to appear earlier than other life-extension technologies.

The use of human stem cells, particularly embryonic stem cells, is controversial. Opponents' objections generally are based on interpretations of religious teachings or ethical considerations. Proponents of stem cell research point out that cells are routinely formed and destroyed in a variety of contexts. Use of stem cells taken from the umbilical cord or parts of the adult body may not provoke controversy.^[19] The controversies over cloning are similar, except general public opinion in most countries stands in opposition to reproductive cloning. Some proponents of therapeutic cloning predict the production of whole bodies, lacking consciousness, for eventual brain transplantation.

[edit] Cryonics

For cryonicists (advocates of cryopreservation), storing the body at low temperatures after death may provide an "ambulance" into a future in which advanced medical technologies may allow resuscitation and repair. They speculate cryogenic temperatures will minimise changes in biological tissue for many years, giving the medical community ample time to cure all disease, rejuvenate the aged and repair any damage that is caused by the cryopreservation process.

Cryonicists do not believe that legal death is "real death" because stoppage of heartbeat and breathing, the usual criteria for legal death, occur before biological death of cells and tissues of the body. Even at room temperature, cells may take hours to die and days to decompose. Although neurological damage occurs within 4–6 minutes of cardiac arrest, the irreversible neurodegenerative processes do not manifest for hours.^[20] They state that rapid cooling and cardio-pulmonary support applied immediately after pronouncement of death can preserve cells and tissues for long-term preservation at cryogenic temperatures. People, especially children, have survived up to an hour without heartbeat after having fallen into ice water. In one case, full recovery was reported after 45 minutes underwater.^[21] To facilitate rapid preservation of cells and tissue, cryonics "standby teams" wait by the bedside of patients who wish to be cryopreserved to apply cooling and cardio-pulmonary support as soon as possible after declaration of death.

No mammal has been cryopreserved and brought back to life, and cryonics is not currently accepted by science. Some individual scientists support the idea based on their expectations of the capabilities of future science.^[22]

[edit] Theoretical combination strategies

Using combinations of existing and predicted future biochemical and genetic techniques has also been proposed. One such theoretical strategy proposes a cure for cancer, stem cell treatments, addition of new enzymes to the human body and moving mitochondrial DNA to the cellular nucleus.^[23] This proposal is said to lack scientific evidence^[4] and has been called pseudoscientific because its proposed techniques are speculative.^[2]

[edit] 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. However, it is not understood how consciousness exists, and there is no existing technology for "reading" the "contents" of a human mind. Futurist Ray Kurzweil predicts that computer hardware will be powerful enough to run a functional model of the human mind by the 2020s.

If the mind's contents could be read and transferred, would the personal identity of the original human be retained? And what would be the status of personal identity after duplication? A possible solution to the first objection is to interface biological humans brains with computer parts, and the gradual replacement of biological components with mechanical ones — functionally no different to the biological renewal of synapses. The philosophical Ship of Theseus enigma still remains with this solution.

The difficulty in seeing mind uploading as a solution is along the same lines of mind cloning and transporter duality paradox. The situation is contemplated where the mind is uploaded, yet the original mind remains. In this case, the person will still be themselves, and the clone will be alien to them, and vice versa. The biological mind would view itself as the original, but would die. The computer mind would view itself as original yet artificial. If the clone is a separate individual, then the consciousness of the original would still die. Even in the case where there is never a clone (killing the original upon mind uploading, or the gradual replacement of biological components) while the distinction would be less apparent, it would still be applicable in some regards. Many regard the proposed existence of the human soul as an insurmountable barrier for uploading as well. There is also the materialist criticism that a copy can never be the original by definition.

[edit] Nanomedicine

Some, such as Robert Freitas, Ray Kurzweil, and others, have proposed that nanorobots could perform cellular repair in vivo, which could reverse damage from aging at the molecular level, restoring youth and giving a potentially indefinite lifespan. These proposals however rely on the as-of-yet highly speculative hypothetical technology of molecular manufacturing, so the feasibility of this is highly contentious.

[edit] Genetic Modification

Gene therapy, in which artificial genes are inserted into an organism to replace mutated or otherwise deficient genes, has been proposed as a future strategy to prevent aging.^[24][25]. Targeting catalase to the mitochondria resulted in a 20% lifespan increase in transgenic mice, and improved performance in AAV therapeutically infected mice.^[26]

[edit] 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.

Saul Kent published The Life Extension Revolution (ISBN 0-688-03580-9) in 1980 and created a nutraceutical firm called the Life Extension Foundation, a non-profit organization that promotes supplements. The Life Extension Foundation publishes a periodical called Life Extension Magazine. The 1982 bestselling book Life Extension: A Practical Scientific Approach (ISBN 0-446-51229-X) by Durk Pearson and Sandy Shaw further popularized the phrase "life extension".

Money generated by the non-profit 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 baseball star Ted Williams was cryonically preserved by Alcor in 2002 and a family dispute arose as to whether Williams had really wanted to be cryopreserved.

In 1983, Roy Walford, a life-extensionist and gerontologist, published a popular book called Maximum Lifespan. In 1988, Walford and his student Richard Weindruch summarized their research into the ability of calorie restriction to extend the lifespan of rodents in The Retardation of Aging and Disease by Dietary Restriction (ISBN 0-398-05496-7). 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 practiced calorie restriction himself. Walford died at the age of 80 from complications caused by amyotrophic lateral sclerosis.

Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension Foundation have included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon, the principals of the Foundation, were jailed. The LEF has accused the FDA of perpetrating a "Holocaust" and "seeking gestapo-like power" through its regulation of drugs and marketing claims.^[27]

In 1992, the American Academy of Anti-Aging Medicine (A4M) was formed to create what it considered an anti-aging medical specialty distinct from geriatrics, and to hold trade shows for physicians interested in anti-aging medicine. The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing.^[28]

[edit] Ethics and politics of life extension

Leon Kass (chairman of the US President's Council on Bioethics from 2001 to 2005) has questioned whether potential exacerbation of overpopulation problems would make life extension unethical.^[29] He states his opposition to life extension with the words:

"simply to covet a prolonged life span for ourselves is both a sign and a cause of our failure to open ourselves to procreation and to any higher purpose. …[The] desire to prolong youthfulness is not only a childish desire to eat one's life and keep it; it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity."^[30]

Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few.^[31] In an extended metaphor entitled "The Fable of the Dragon-Tyrant", Bostrom envisions death as a monstrous dragon who demands human sacrifices. In the fable, after a lengthy debate between those who believe the dragon is a fact of life and those who believe the dragon can and should be destroyed, the dragon is finally killed. Bostrom argues that political inaction allowed many preventable human deaths to occur.^[32]

[edit] See also

• Advanced glycation end product
• Bioethics
• Raw foodism

[edit] References

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[edit] Further reading

Books

• Biological Aging Measurement. Clinical Applications. Ward Dean, M.D. The Center for Bio-Gerontology. 1988. Paperback, 426pp. ISBN 0-937777-00-5
• The Biology of Life Span: A Quantitative Approach. Leonid A. Gavrilov & Natalia S. Gavrilova (1991), New York: Harwood Academic Publisher, ISBN 3-7186-4983-7
• Brain Boosters. Foods And Drugs That Make You Smarter. (A quote from the book: "It's hard to distinguish between the health and anti-aging uses of the smart drugs and nutrients.") Beverly Potter & Sebastian Orfali. Ronin Publishing. 1993. Paperback, 257 pages. ISBN 0-914171-65-8
• Brain Fitness. Anti-Aging Strategies To Fight Alzheimer's Disease, Supercharge Your Memory, Sharpen Your Intelligence, De-Stress Your Mind, Control Mood Swings, and Much More… Robert Goldman, M.D, D.O., Ph.D., With Ronald Klatz, M.D., D.O., and Liza Berger. Doubleday. 1995. Paperpack, 346pp. ISBN 0385488696
• The Directory of Life Extension Supplements. Life Extension Foundation. Published annually.
• Fantastic Voyage: The Science Behind Radical Life Extension Raymond Kurzweil and Terry Grossman M.D., Rodale. 2004. 452pp. ISBN 1-57954-954-3
• 50 Simple Ways To Live A Longer Life: Everyday Techniques From The Forefront Of Science. Suzanne Bohan and Glenn Thompson. Sourcebooks. 2005. Paperback, 287 pages. ISBN 1-4022-0375-6
• Formula for Life. The Definitive Book on Correct Nutrition, Anti-Oxidants and Vitamins, Disease Prevention, and Longevity. Eberhard Kronhausen, Ed. D, and Phyllis Kronhausen Ed. D., with Harry B. Demopoulos, M.D. William Morrow and Company. 1989. Paperback, 622 pages. ISBN 0-688-09426-0
• How To Live Longer And Feel Better. Linus Pauling. W.H. Freeman and Company. 1986. Paperback, 413 pages. ISBN 0-380-70289-4
• Life Extension. A Practical Scientific Approach. Adding Years to Your Life and Life to Your Years. Durk Pearson and Sandy Shaw. Warner Books. 1982. Hardcover, 858pp. ISBN 0-446-51229-X
• The Life Extension Companion. The Latest Breakthroughs in Health Science. Durk Pearson and Sandy Shaw. Warner Books. 1984. Hardcover, 430 pages. ISBN 0-446-51277-X
• The Life Extension Revolution: The Definitive Guide to Better Health, Longer Life, and Physical Immortality. Saul Kent. 1980. Hard Cover. ISBN 0-688-03580-9
• The Life Extension Revolution: The New Science of Growing Older Without Aging. Philip Lee, M.D. and Monica Reinagel Miller. Bantam. 2005. Hardcover, (416 pages). ISBN 0-553-80353-0
• The Life Extension Weight Loss Programme. Durk Pearson and Sandy Shaw.
• LifeSpan-Plus. 900 Natural Techniques To Live Longer. Rejuvenate Your Heart; Stay Infection-Free; Prevent a Stroke; Reduce Stress; Control Your Blood Pressure; Strengthen Your Bones; Eliminate Body Toxins. By the editors of Prevention Magazine. Rodale. 1990. Hardcover, 422 pages. ISBN 0-87857-908-7
• Live Longer Now. The First One Hundred Years Of Your Life. Jon N. Leanard, Jack L. Hofer, and Nathan Pritikin. Grosset and Dunlap. 1974 (predates the life extension movement, and therefore lacks megadosing recommendations.) Paperpack, 232 pages. ISBN 0-441-48514-6
• The Long Tomorrow. Michael Rose. Oxford University Press. 2005. ISBN 0195179390
• Merchants of Immortality. Chasing The Dream Of Human Life Extension. Stephen S. Hall. Houghton Mifflin Company. 2003. Paperback, 439 pp. ISBN 0-618-49221-6
• Mind Food and Smart Pills. How To Increase Your Intelligence and Prevent Brain Aging. Ross Pelton. 1986. Paperback, 170pp. ISBN 0-936809-00-0
• No More Dying. The Conquest Of Aging And The Extension Of Human Life. Joel Kurtzman and Phillip Gordon. Dell. 1976. Paperpback, 252 pages. ISBN 0-440-36247-4
• Prevention's The Sugar Solution. Edited by Sari Harrar, Prevention Health News Editor. Rodale. 2005. Hardcover, 406 pages. ISBN 1-57954-912-8
• Secrets of Life Extension. How to halt or reverse the aging process and live a long and healthy life. You can extend the rest of your life. All the new scientific breakthroughs John A. Mann. Bantam Books. 1980. Paperback, 296 pages. ISBN 0-55323-450-1
• Nutrition Against Disease. Dr. Roger J. Williams. Pitman Publishing Corporation. 1971 (predates megadosing). 370 pages. ISBN 0273318500
• Smart Drugs & Nutrients. How To Improve Your Membory And Increase Your Intelligence Using The Latest Discoveries In Neuroscience. (Many of the substances in this book have life-extending or cell regenerating effects.) Ward Dean, M.D. and Joh Morgenthaler. B&J Publications. 1990. Paperback, 222pp. ISBN 0962741892
• Smart Drugs II: The Next Generation : New Drugs and Nutrients to Improve Your Memory and Increase Your Intelligence. Ward Dean (M.D.), John Morgenthaler, Steven Wm Fowkes. Smart Publications. 1993. Paperback, 287 pages. ISBN 0-9627418-7-6
• Stop Aging Now! The Ultimate Plan For Staying Young & Reversing The Aging Process. Based On Cutting-Edge Research Revealing The Amazing Antiaging Powers Of Supplements, Herbs, & Food. Jean Carper. Harper Perennial. 1995. Paperback, 372pp. ISBN 0-06-098500-3
• Stop the FDA. Save Your Health Freedom. Articles by Linus Pauling, PhD; Abram Hoffer, MD; Ward Dean, MD; Senator Orrin Hatch; Durk Pearson and Sandy Shaw; and many more. (Many essays on health politics, by various leaders of the Life Extension Movement). Edited by John Morgenthaler & Steven Wm. Fowkes. Health Freedom Publications. 1992. Paperback, 186pp. ISBN 0-9627418-8-4
• The Wrinkle Cure. The All-Natural Formula for Stopping Time. Unlock the Power of Cosmeceuticals for Supple, Youthful Skin. Nicholas Perricone, M.D. Rodale. 2000. Hardcover, 208 pages. ISBN 1-57954-237-9
• Your Personal Life-Extension Program. A Practical Guide to the New Science That Can Make You Stronger, Smarter, Sexier, More Energetic, and More Youthful. Saul Kent. Morrow. 1985. Hardcover, 384 pages. ISBN 0-688-00629-9

Scientific Journals

• Holzenberger M, Dupont J, Ducos B, et al. (January 2003). "IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice". Nature 421 (6919): 182–7. doi:10.1038/nature01298. PMID 12483226. 
• http://dovepress.com/articles.php?journal_id=63^{[dead link]} Clinical Interventions in Aging Editor-in-Chief: Dr Richard F Walker. Publisher: Dove Medical Press Ltd. ISSN 1176-9092. Published Quarterly
• Rejuvenation Research Editor: Aubrey de Grey. Publisher: Mary Ann Liebert, Inc. ISSN 1549-1684 - Published Quarterly

[edit] External links

• Aging Research Centre
• Aubrey de Grey: 'We will be able to live to 1,000'
• Immortality Institute
• Kurzweil Biomed/Life Extension News
• Longevity Meme
• Vitae Institute non-profit for developing life-extension technology through basic research
• Why We Age - An Anti-aging and Longevity Research Resource
• The British Longevity Society