From Wikipedia, the free encyclopedia
Life extension science, also known as anti-aging medicine, indefinite life extension, experimental gerontology, and biomedical gerontology, is the study of slowing down or reversing the processes of aging to extend both the maximum and average lifespan. Some researchers in this area, and "life extensionists", "immortalists" or "longevists" (those who wish to achieve longer lives themselves), believe that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, pharmaceuticals, and organ replacement (such as with artificial organs or xenotransplantations) will eventually enable humans to have indefinite lifespans (agerasia[1]) through complete rejuvenation to a healthy youthful condition.
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.[2] Some medical experts state that the use of such products has not been proven to affect the aging process and many claims regarding the efficacy of these marketed products have been roundly criticized by medical experts, including the American Medical Association.[2][3][4][5][6]
However, it has not been shown that the goal of indefinite human lifespans itself is necessarily unfeasible; some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.[7][8][9][10] The ethical ramifications of life extension are debated by bioethicists.
A Spring 2013 Pew Research poll in the United States found that 38% of Americans would want life extension treatments, and 56% would reject it. However, it also found that 68% believed most people would want it and that only 4% consider an "ideal lifespan" to be more than 120 years. The median "ideal lifespan" was 91 years of age and the majority of the public (63%) viewed medical advances aimed at prolonging life as generally good. 41% of Americans believed that radical life extension would be good for society, while 51% said they believed it would be bad for society.[12] One possibility for why 56% of Americans claim they would reject life extension treatments may be due to the cultural perception that living longer would result in a longer period of decrepitude, and that the elderly in our current society are unhealthy.[14]
The longest a human has ever been proven to live is 122 years, the case of Jeanne Calment who was born in 1875 and died in 1997, whereas the maximum lifespan of a wildtype mouse, commonly used as a model in research on aging, is about three years.[18] Genetic differences between humans and mice that may account for these different aging rates include differences in efficiency of DNA repair, antioxidant defenses, energy metabolism, proteostasis maintenance, and recycling mechanisms such as autophagy.[19]
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 access to improved medical care, vaccinations, 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. Widely recognized methods of extending maximum lifespan in model organisms such as nematodes, fruit flies, and mice include caloric restriction, gene manipulation, and administration of pharmaceuticals.[20] Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality.[21][22]
Theoretically, extension of maximum lifespan in humans could be achieved by reducing the rate of aging damage by periodic replacement of damaged tissues, molecular repair or rejuvenation of deteriorated cells and tissues, reversal of harmful epigenetic changes, or the enhancement of telomerase enzyme activity.[23][24]
Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions. As of 2009, investigators had founds ways to increase the lifespan of nematode worms and yeast by 10-fold; the record in nematodes was achieved through genetic engineering and the extension in yeast by a combination of genetic engineering and caloric restriction.[25] A 2009 review of longevity research noted: "Extrapolation from worms to mammals is risky at best, and it cannot be assumed that interventions will result in comparable life extension factors. Longevity gains from dietary restriction, or from mutations studied previously, yield smaller benefits to Drosophila than to nematodes, and smaller still to mammals. This is not unexpected, since mammals have evolved to live many times the worm's lifespan, and humans live nearly twice as long as the next longest-lived primate. From an evolutionary perspective, mammals and their ancestors have already undergone several hundred million years of natural selection favoring traits that could directly or indirectly favor increased longevity, and may thus have already settled on gene sequences that promote lifespan. Moreover, the very notion of a “life-extension factor” that could apply across taxa presumes a linear response rarely seen in biology."[25]
Preliminary studies of caloric restriction on humans using surrogate measurements have provided evidence that caloric restriction may have powerful protective effect against secondary aging in humans. Caloric restriction in humans may reduce the risk of developing Type 2 diabetes and atherosclerosis.[28] More research is needed.
The free-radical theory of aging suggests that antioxidant supplements, such as Vitamin C, Vitamin E, Q10, lipoic acid, carnosine, and N-acetylcysteine, might extend human life. However, combined evidence from several clinical trials suggest that β-Carotene supplements and high doses of Vitamin E increase mortality rates.[29] Resveratrol is a sirtuin stimulant that has been shown to extend life in animal models, but the effect of resveratrol on lifespan in humans is unclear as of 2011.[30]
There are many traditional herbs purportedly used to extend the health-span, including a Chinese tea called Jiaogulan (Gynostemma pentaphyllum), dubbed "China's Immortality Herb."[31] Ayurveda, the traditional Indian system of medicine, describes a class of longevity herbs called rasayanas, including Bacopa monnieri, Ocimum sanctum, Curcuma longa, Centella asiatica, Phyllanthus emblica, Withania somnifera and many others.[31]
Although some recent clinical studies have shown that low-dose growth hormone (GH) treatment for adults with GH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, increasing bone density and muscle strength, improves cardiovascular parameters (i.e. decrease of LDL cholesterol), and affects the quality of life without significant side effects,[32][33][34] the evidence for use of growth hormone as an anti-aging therapy is mixed and based on animal studies. An early study suggested that supplementation of mice with growth hormone increased average life expectancy.[35] 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.[36] Furthermore, mouse models lacking the insulin-like growth factor also live especially long and have low levels of growth hormone.[36]
In the United States, product claims on food and drug labels are strictly regulated. The First Amendment (freedom of speech) protects third-party publishers' rights to distribute fact, opinion and speculation on life extension practices. Manufacturers and suppliers also provide informational publications, but because they market the substances, they are subject to monitoring and enforcement by the Federal Trade Commission (FTC), which polices claims by marketers. What constitutes the difference between truthful and false claims is hotly debated and is a central controversy in this arena.[citation needed]
Two drugs that may have potential benefits of combating age-related maladies are resveratrol and rapamycin. These drugs are considered to be the forefront drugs in anti-aging research.[43] Before these drugs had been tested, the best-characterized anti-aging therapy was, and still is, CR. In some studies calorie restriction has been shown to extend the life of mice, yeast, and rhesus monkeys significantly.[44][45] However, a more recent study has shown that in contrast, calorie restriction has not improved the survival rate in rhesus monkeys.[46] Long-term human trials of CR are now being done. It is the hope of the anti-aging researchers that resveratrol and rapamycin may act as CR mimetics to increase the life span of humans.[43]
Resveratrol was first thought to be an activator of sirtuins, a family of deacetylases, that would promote anti aging effects without having to restrict caloric intake.[47] However, recent replication studies have failed to show that Resveratrol increases the life span in yeast or mice and that Resveratrol may not activate sirtuins that are biologically beneficial to age reduction.[48][49][50][51] Another study was done showing that resveratrol activates or inhibits fifteen or more different enzymes.[52] Of those enzymes, one stands out with potential for reducing age-related disease. AMP-activated protein kinase (AMPK) has shown to increase life span of nematodes and prevent obesity in mice.[53] Although resveratrol has not been proven to extend the life-span of mammals at the current doses tested, resveratrol could be used to access some of the same molecular pathways that CR does. Several examples would include diet induced obesity, some cancers, cardiovascular disease, and neurodegenerative diseases.[54]
While resveratrol has not been proven to increase life span, rapamycin has shown much more promise.[43] Rapamycin is shown to increase longevity by inhibiting the mammalian target of rapamycin (mTOR) the same way CR does.[55] Study systems including yeast, nematodes, flies, and mammals, have shown that reduction of TOR signaling will result in an increased life span.[56][40] Additionally, rapamycin has similar effects of resveratrol in protecting against several cancers, cardiovascular, and neurodegenerative diseases.[43][56] Rapamycin also has been shown to act as an immunosuppressant, however more testing is needed to show if the life extending dose comes at the cost of an impaired immune system.[56]
Resveratrol and rapamycin have both shown protection against cancers, cardiovascular disease, and neurodegenerative diseases in multiple study systems.[54][56] Rapamycin looks to have more potential in life span extension than resveratrol, but may come at a price of immune system impairment.[43][56] Clinical trials are now being performed to see if rapamycin or resveratrol will have anti-aging effects in humans.
Other attempts to create anti-aging drugs have taken different research paths. One notable direction of research has been research into the possibility of using the enzyme telomerase in order to counter the process of telomere shortening.[57] However, there are potential dangers in this, since some research has also linked telomerase to cancer and to tumor growth and formation.[58]
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.[62]
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.
Many cryonicists do not believe that legal death is "real death" because stoppage of heartbeat and breathing—the usual medical 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.[64] Cryonicists state that rapid cooling and cardio-pulmonary support applied immediately after certification of death can preserve cells and tissues for long-term preservation at cryogenic temperatures. People, particularly children, have survived up to an hour without heartbeat after submersion in ice water. In one case, full recovery was reported after 45 minutes underwater.[65] To facilitate rapid preservation of cells and tissue, cryonics "standby teams" are available to wait by the bedside of patients who are to be cryopreserved to apply cooling and cardio-pulmonary support as soon as possible after declaration of death.[66]
No mammal has been successfully cryopreserved and brought back to life, with the exception of frozen human embryos. Resuscitation of a postembryonic human from cryonics is not possible with current science. Some scientists still support the idea based on their expectations of the capabilities of future science.[67][68]
While many biogerontologists find these ideas "worthy of discussion"[70][71] and SENS conferences feature important research in the field,[72][73] some contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science".[3][5]
A large array of genetic modifications have been found to increase lifespan in model organisms such as yeast, nematode worms, fruit flies, and mice. As of 2013, the longest extension of life caused by a single gene manipulation was roughly 150% in mice and 10-fold in nematode worms.[76]
In 1976, futurists Joel Kurtzman and Philip Gordon wrote No More Dying. The Conquest Of Aging And The Extension Of Human Life, (ISBN 0-440-36247-4) the first popular book on research to extend human lifespan. Subsequently, Kurtzman was invited to testify before the House Select Committee on Aging, chaired by Claude Pepper of Florida, to discuss the impact of life extension on the Social Security system.
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 dietary 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".
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.[citation needed] 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.
Money generated by the non-profit Life Extension Foundation allowed Saul Kent to finance the Alcor Life Extension Foundation, the world's 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.
Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension Foundation included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon, the principals of the Foundation, were jailed. The LEF accused the FDA of perpetrating a "Holocaust" and "seeking gestapo-like power" through its regulation of drugs and marketing claims.[84]
In 2003, Doubleday published "The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging," by Michael D. West. West emphasised the potential role of embryonic stem cells in life extension.[85]
In 2003, Aubrey de Grey and David Gobel formed the Methuselah Foundation, which gives financial grants to anti-aging research projects. In 2009, de Grey and several others founded the SENS Research Foundation, a California-based scientific research organization which conducts research into aging and funds other anti-aging research projects at various universities.[88] In 2013, Google announced Calico, a new company based in San Francisco that will harness new technologies to increase scientific understanding of the biology of aging.[89] It is led by Arthur D. Levinson,[90] and its research team includes scientists such as Hal V. Barron, David Botstein, and Cynthia Kenyon. In 2014, biologist Craig Venter founded Human Longevity Inc., a company dedicated to scientific research to end aging through genomics and cell therapy. It subsequently began building the a human genotype, microbiome, and phenotype database in the world to aid in its research.[91]
Aside from private initiatives, aging research is being conducted in university laboratories, and includes universities such as Harvard and UCLA. University researchers have made a number of breakthroughs in extending the lives of mice and insects by reversing certain aspects of aging.[92][93][94][95]
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.[99] He states his opposition to life extension with the words:
Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few.[102] 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.[103]
The discussion whether aging should be viewed as a disease or not has important implications. It would stimulate pharmaceutical companies to develop life extension therapies and in the United States of America, it would also increase the regulation of the anti-aging market by the FDA. Anti-aging now falls under the regulations for cosmetic medicine which are less tight than those for drugs.[108][110]
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.[2] Some medical experts state that the use of such products has not been proven to affect the aging process and many claims regarding the efficacy of these marketed products have been roundly criticized by medical experts, including the American Medical Association.[2][3][4][5][6]
However, it has not been shown that the goal of indefinite human lifespans itself is necessarily unfeasible; some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.[7][8][9][10] The ethical ramifications of life extension are debated by bioethicists.
Public opinion
Life extension is a controversial topic due to fear of overpopulation and possible effects on society.[11] Religious people are no more likely to oppose life extension than the unaffiliated,[12] though some variation exists between religious denominations. Blacks and Hispanics are more likely to support life extension than white people.[12] Biogerontologist Aubrey De Grey counters the overpopulation critique by pointing out that the therapy could postpone or eliminate menopause, allowing women to space out their pregnancies over more years and thus decreasing the yearly population growth rate.[13] Moreover, the philosopher and futurist Max More argues that, given the fact the worldwide population growth rate is slowing down and is projected to eventually stabilize and begin falling, superlongevity would be unlikely to contribute to overpopulation.[11]A Spring 2013 Pew Research poll in the United States found that 38% of Americans would want life extension treatments, and 56% would reject it. However, it also found that 68% believed most people would want it and that only 4% consider an "ideal lifespan" to be more than 120 years. The median "ideal lifespan" was 91 years of age and the majority of the public (63%) viewed medical advances aimed at prolonging life as generally good. 41% of Americans believed that radical life extension would be good for society, while 51% said they believed it would be bad for society.[12] One possibility for why 56% of Americans claim they would reject life extension treatments may be due to the cultural perception that living longer would result in a longer period of decrepitude, and that the elderly in our current society are unhealthy.[14]
Average and maximum lifespans
During the process of aging, an organism accumulates damage to its macromolecules, cells, tissues, and organs. Specifically, aging is characterized as and thought to be caused by "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication."[15] Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well.[16][16][17]The longest a human has ever been proven to live is 122 years, the case of Jeanne Calment who was born in 1875 and died in 1997, whereas the maximum lifespan of a wildtype mouse, commonly used as a model in research on aging, is about three years.[18] Genetic differences between humans and mice that may account for these different aging rates include differences in efficiency of DNA repair, antioxidant defenses, energy metabolism, proteostasis maintenance, and recycling mechanisms such as autophagy.[19]
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 access to improved medical care, vaccinations, 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. Widely recognized methods of extending maximum lifespan in model organisms such as nematodes, fruit flies, and mice include caloric restriction, gene manipulation, and administration of pharmaceuticals.[20] Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality.[21][22]
Theoretically, extension of maximum lifespan in humans could be achieved by reducing the rate of aging damage by periodic replacement of damaged tissues, molecular repair or rejuvenation of deteriorated cells and tissues, reversal of harmful epigenetic changes, or the enhancement of telomerase enzyme activity.[23][24]
Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions. As of 2009, investigators had founds ways to increase the lifespan of nematode worms and yeast by 10-fold; the record in nematodes was achieved through genetic engineering and the extension in yeast by a combination of genetic engineering and caloric restriction.[25] A 2009 review of longevity research noted: "Extrapolation from worms to mammals is risky at best, and it cannot be assumed that interventions will result in comparable life extension factors. Longevity gains from dietary restriction, or from mutations studied previously, yield smaller benefits to Drosophila than to nematodes, and smaller still to mammals. This is not unexpected, since mammals have evolved to live many times the worm's lifespan, and humans live nearly twice as long as the next longest-lived primate. From an evolutionary perspective, mammals and their ancestors have already undergone several hundred million years of natural selection favoring traits that could directly or indirectly favor increased longevity, and may thus have already settled on gene sequences that promote lifespan. Moreover, the very notion of a “life-extension factor” that could apply across taxa presumes a linear response rarely seen in biology."[25]
Current anti-aging strategies and issues
Diets and supplements
Much life extension research focuses on nutrition—diets or supplements—as a means to extend lifespan, although few of these have been systematically tested for significant longevity effects. The many diets promoted by anti-aging advocates are often contradictory.[original research?] A dietary pattern with some support from scientific research is caloric restriction.[26][27]Preliminary studies of caloric restriction on humans using surrogate measurements have provided evidence that caloric restriction may have powerful protective effect against secondary aging in humans. Caloric restriction in humans may reduce the risk of developing Type 2 diabetes and atherosclerosis.[28] More research is needed.
The free-radical theory of aging suggests that antioxidant supplements, such as Vitamin C, Vitamin E, Q10, lipoic acid, carnosine, and N-acetylcysteine, might extend human life. However, combined evidence from several clinical trials suggest that β-Carotene supplements and high doses of Vitamin E increase mortality rates.[29] Resveratrol is a sirtuin stimulant that has been shown to extend life in animal models, but the effect of resveratrol on lifespan in humans is unclear as of 2011.[30]
There are many traditional herbs purportedly used to extend the health-span, including a Chinese tea called Jiaogulan (Gynostemma pentaphyllum), dubbed "China's Immortality Herb."[31] Ayurveda, the traditional Indian system of medicine, describes a class of longevity herbs called rasayanas, including Bacopa monnieri, Ocimum sanctum, Curcuma longa, Centella asiatica, Phyllanthus emblica, Withania somnifera and many others.[31]
Hormone treatments
The anti-aging industry offers several hormone therapies. Some of these have been criticized for possible dangers to the patient and a lack of proven effect. For example, the American Medical Association has been critical of some anti-aging hormone therapies.[2]Although some recent clinical studies have shown that low-dose growth hormone (GH) treatment for adults with GH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, increasing bone density and muscle strength, improves cardiovascular parameters (i.e. decrease of LDL cholesterol), and affects the quality of life without significant side effects,[32][33][34] the evidence for use of growth hormone as an anti-aging therapy is mixed and based on animal studies. An early study suggested that supplementation of mice with growth hormone increased average life expectancy.[35] 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.[36] Furthermore, mouse models lacking the insulin-like growth factor also live especially long and have low levels of growth hormone.[36]
Insulin like growth factor (IGF-1) restriction
People suffering from a rare condition known as Laron syndrome have a mutation in the gene that makes the receptor for growth hormone. It is theorised that this mutation may hold a key to life extension.Longo said that some level of IGF-1 was necessary to protect against heart disease, but that lowering the level might be beneficial. A drug that does this is already on the market for treatment of acromegaly, a thickening of the bones caused by excessive growth hormone. “Our underlying hypothesis is that this drug would prolong life span,” Longo said. He said he was not taking the drug, called pegvisomant or Somavert, which is very hard to obtain.[37]
Scientific controversy regarding anti-aging nutritional supplementation and medicine
Some critics dispute the portrayal of aging as a disease. For example, Leonard Hayflick, who determined that fibroblasts are limited to around 50 cell divisions, 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.[4]Ethics and politics of anti-aging nutritional supplementation and medicine
Politics relevant to the substances of life extension pertain mostly to communications and availability.[citation needed]In the United States, product claims on food and drug labels are strictly regulated. The First Amendment (freedom of speech) protects third-party publishers' rights to distribute fact, opinion and speculation on life extension practices. Manufacturers and suppliers also provide informational publications, but because they market the substances, they are subject to monitoring and enforcement by the Federal Trade Commission (FTC), which polices claims by marketers. What constitutes the difference between truthful and false claims is hotly debated and is a central controversy in this arena.[citation needed]
Consumer motivations for using anti-aging products
Research by Sobh and Martin (2011) suggests that people buy anti-aging products to obtain a hoped-for self (e.g., keeping a youthful skin) or to avoid a feared-self (e.g., looking old). The research shows that when consumers pursue a hoped-for self, it is expectations of success that most strongly drive their motivation to use the product. The research also shows why doing badly when trying to avoid a feared self is more motivating than doing well. Interestingly, when product use is seen to fail it is more motivating than success when consumers seek to avoid a feared-self.[38]Proposed strategies of life extension
Anti-aging drugs
There are a number of drugs intended to slow the aging process currently being studied in animal models. One type of research is related to the observed effects a calorie restriction (CR) diet, which has been shown to extend lifespan in some animals[39] Based on that research, there have been attempts to develop drugs that will have the same effect on the aging process as a caloric restriction diet, which are known as Caloric restriction mimetic drugs. Drugs that have been studied for possible longevity effects on laboratory animals because of a possible CR-mimic effect include rapamycin,[40] metformin,[41] and resveratrol.[42]Two drugs that may have potential benefits of combating age-related maladies are resveratrol and rapamycin. These drugs are considered to be the forefront drugs in anti-aging research.[43] Before these drugs had been tested, the best-characterized anti-aging therapy was, and still is, CR. In some studies calorie restriction has been shown to extend the life of mice, yeast, and rhesus monkeys significantly.[44][45] However, a more recent study has shown that in contrast, calorie restriction has not improved the survival rate in rhesus monkeys.[46] Long-term human trials of CR are now being done. It is the hope of the anti-aging researchers that resveratrol and rapamycin may act as CR mimetics to increase the life span of humans.[43]
Resveratrol was first thought to be an activator of sirtuins, a family of deacetylases, that would promote anti aging effects without having to restrict caloric intake.[47] However, recent replication studies have failed to show that Resveratrol increases the life span in yeast or mice and that Resveratrol may not activate sirtuins that are biologically beneficial to age reduction.[48][49][50][51] Another study was done showing that resveratrol activates or inhibits fifteen or more different enzymes.[52] Of those enzymes, one stands out with potential for reducing age-related disease. AMP-activated protein kinase (AMPK) has shown to increase life span of nematodes and prevent obesity in mice.[53] Although resveratrol has not been proven to extend the life-span of mammals at the current doses tested, resveratrol could be used to access some of the same molecular pathways that CR does. Several examples would include diet induced obesity, some cancers, cardiovascular disease, and neurodegenerative diseases.[54]
While resveratrol has not been proven to increase life span, rapamycin has shown much more promise.[43] Rapamycin is shown to increase longevity by inhibiting the mammalian target of rapamycin (mTOR) the same way CR does.[55] Study systems including yeast, nematodes, flies, and mammals, have shown that reduction of TOR signaling will result in an increased life span.[56][40] Additionally, rapamycin has similar effects of resveratrol in protecting against several cancers, cardiovascular, and neurodegenerative diseases.[43][56] Rapamycin also has been shown to act as an immunosuppressant, however more testing is needed to show if the life extending dose comes at the cost of an impaired immune system.[56]
Resveratrol and rapamycin have both shown protection against cancers, cardiovascular disease, and neurodegenerative diseases in multiple study systems.[54][56] Rapamycin looks to have more potential in life span extension than resveratrol, but may come at a price of immune system impairment.[43][56] Clinical trials are now being performed to see if rapamycin or resveratrol will have anti-aging effects in humans.
Other attempts to create anti-aging drugs have taken different research paths. One notable direction of research has been research into the possibility of using the enzyme telomerase in order to counter the process of telomere shortening.[57] However, there are potential dangers in this, since some research has also linked telomerase to cancer and to tumor growth and formation.[58]
Nanotechnology
Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair machines, including ones operating within cells and utilizing as yet hypothetical molecular computers, in his 1986 book Engines of Creation. Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030.[59]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. Recently, the US Department of Defense initiated a program to research the possibility of growing human body parts on mice.[60] Complex biological structures, such as mammalian joints and limbs, have not yet been replicated. 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. As of 2006, the implantation of bio-engineered bladders grown from patients' own cells has proven to be a viable treatment for bladder disease.[61] 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.[62]
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.
Cyborgs
Replacement of biological (susceptible on diseases) organs with mechanical ones could extend life. This is the goal of 2045 Initiative.[63]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 minimize 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.Many cryonicists do not believe that legal death is "real death" because stoppage of heartbeat and breathing—the usual medical 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.[64] Cryonicists state that rapid cooling and cardio-pulmonary support applied immediately after certification of death can preserve cells and tissues for long-term preservation at cryogenic temperatures. People, particularly children, have survived up to an hour without heartbeat after submersion in ice water. In one case, full recovery was reported after 45 minutes underwater.[65] To facilitate rapid preservation of cells and tissue, cryonics "standby teams" are available to wait by the bedside of patients who are to be cryopreserved to apply cooling and cardio-pulmonary support as soon as possible after declaration of death.[66]
No mammal has been successfully cryopreserved and brought back to life, with the exception of frozen human embryos. Resuscitation of a postembryonic human from cryonics is not possible with current science. Some scientists still support the idea based on their expectations of the capabilities of future science.[67][68]
Strategies for Engineered Negligible Senescence (SENS)
Another proposed life extension technology would combine existing and predicted future biochemical and genetic techniques. SENS proposes that rejuvenation may be obtained by removing aging damage via the use of stem cells and tissue engineering, removal of telomere-lengthening machinery, allotopic expression of mitochondrial proteins, targeted ablation of cells, immunotherapeutic clearance, and novel lysosomal hydrolases.[69]While many biogerontologists find these ideas "worthy of discussion"[70][71] and SENS conferences feature important research in the field,[72][73] some contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science".[3][5]
Genetic modification
Gene therapy, in which nucleic acid polymers are delivered as a drug and are either expressed as proteins, interfere with the expression of proteins, or correct genetic mutations, has been proposed as a future strategy to prevent aging.[74][75]A large array of genetic modifications have been found to increase lifespan in model organisms such as yeast, nematode worms, fruit flies, and mice. As of 2013, the longest extension of life caused by a single gene manipulation was roughly 150% in mice and 10-fold in nematode worms.[76]
Fooling genes
In The Selfish Gene, Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young.[77] Dawkins attributes inspiration for this idea to Peter Medawar. The basic idea is that our bodies are composed of genes that activate throughout our lifetimes, some when we are young and others when we are older. Presumably, these genes are activated by environmental factors, and the changes caused by these genes activating can be lethal. It is a statistical certainty that we possess more lethal genes that activate in later life than in early life. Therefore, to extend life, we should be able to prevent these genes from switching on, and we should be able to do so by "identifying changes in the internal chemical environment of a body that take place during aging... and by simulating the superficial chemical properties of a young body".[78]Reversal of informational entropy
According to some lines of thinking, the ageing process is routed into a basic reduction of biological complexity,[79] and thus loss of information. In order to reverse this loss, gerontologist Marios Kyriazis suggested that it is necessary to increase input of actionable and meaningful information both individually (into individual brains),[80] and collectively (into societal systems).[81] This technique enhances overall biological function through up-regulation of immune, hormonal, antioxidant and other parameters, resulting in improved age-repair mechanisms. Working in parallel with natural evolutionary mechanisms that can facilitate survival through increased fitness, Kyriazis claims that the technique may lead to a reduction of the rate of death as a function of age, i.e. indefinite lifespan.[82]Mind uploading
One hypothetical future strategy that, as some suggest, "eliminates" the complications related to a physical body, involves the copying or transferring (e.g. by progressively replacing neurons with transistors) of a conscious mind from a biological brain to a non-biological computer system or computational device. The basic idea is to scan the structure of a particular brain in detail, and then construct a software model of it that is so faithful to the original that, when run on appropriate hardware, it will behave in essentially the same way as the original brain.[83] Whether or not an exact copy of one's mind constitutes actual life extension is matter of debate.History of 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.In 1976, futurists Joel Kurtzman and Philip Gordon wrote No More Dying. The Conquest Of Aging And The Extension Of Human Life, (ISBN 0-440-36247-4) the first popular book on research to extend human lifespan. Subsequently, Kurtzman was invited to testify before the House Select Committee on Aging, chaired by Claude Pepper of Florida, to discuss the impact of life extension on the Social Security system.
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 dietary 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".
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.[citation needed] 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.
Money generated by the non-profit Life Extension Foundation allowed Saul Kent to finance the Alcor Life Extension Foundation, the world's 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.
Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension Foundation included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon, the principals of the Foundation, were jailed. The LEF accused the FDA of perpetrating a "Holocaust" and "seeking gestapo-like power" through its regulation of drugs and marketing claims.[84]
In 2003, Doubleday published "The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging," by Michael D. West. West emphasised the potential role of embryonic stem cells in life extension.[85]
Scientific research
In 1991, the American Academy of Anti-Aging Medicine (A4M) was formed as a non-profit organization 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 A4M trains doctors in anti-aging medicine and publicly promotes the field of anti-aging research. It has about 26,000 members, of whom about 97% are doctors and scientists.[86] The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing.[87]In 2003, Aubrey de Grey and David Gobel formed the Methuselah Foundation, which gives financial grants to anti-aging research projects. In 2009, de Grey and several others founded the SENS Research Foundation, a California-based scientific research organization which conducts research into aging and funds other anti-aging research projects at various universities.[88] In 2013, Google announced Calico, a new company based in San Francisco that will harness new technologies to increase scientific understanding of the biology of aging.[89] It is led by Arthur D. Levinson,[90] and its research team includes scientists such as Hal V. Barron, David Botstein, and Cynthia Kenyon. In 2014, biologist Craig Venter founded Human Longevity Inc., a company dedicated to scientific research to end aging through genomics and cell therapy. It subsequently began building the a human genotype, microbiome, and phenotype database in the world to aid in its research.[91]
Aside from private initiatives, aging research is being conducted in university laboratories, and includes universities such as Harvard and UCLA. University researchers have made a number of breakthroughs in extending the lives of mice and insects by reversing certain aspects of aging.[92][93][94][95]
Ethics and politics of life extension
Though many scientists state[96] that life extension and radical life extension are possible, there are still no international or national programs focused on radical life extension. There are political forces staying for and against life extension. By 2012, in Russia, the United States, Israel, and the Netherlands, the Longevity political parties started. They aimed to provide political support to radical life extension research and technologies, and ensure the fastest possible and at the same time soft transition of society to the next step - life without aging and with radical life extension, and to provide access to such technologies to most currently living people.[97] [98]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.[99] 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."[100]John Harris, former editor-in-chief of the Journal of Medical Ethics, argues that as long as life is worth living, according to the person himself, we have a powerful moral imperative to save the life and thus to develop and offer life extension therapies to those who want them.[101]
Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few.[102] 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.[103]
Aging as a disease
Most mainstream medical organizations and practitioners do not consider aging to be a disease. David Sinclair says: "I don't see aging as a disease, but as a collection of quite predictable diseases caused by the deterioration of the body".[104] The two main arguments used are that aging is both inevitable and universal while diseases are not.[105] However not everyone agrees. Harry R. Moody, Director of Academic Affairs for AARP, notes that what is normal and what is disease strongly depends on a historical context.[106] David Gems, Assistant Director of the Institute of Healthy Ageing, strongly argues that aging should be viewed as a disease.[107] In response to the universality of aging, David Gems notes that it is as misleading as arguing that Basenji are not dogs because they do not bark.[108] Because of the universality of aging he calls it a 'special sort of disease'. Robert M. Perlman, coined the terms ‘aging syndrome’ and ‘disease complex’ in 1954 to describe aging.[109]The discussion whether aging should be viewed as a disease or not has important implications. It would stimulate pharmaceutical companies to develop life extension therapies and in the United States of America, it would also increase the regulation of the anti-aging market by the FDA. Anti-aging now falls under the regulations for cosmetic medicine which are less tight than those for drugs.[108][110]
