Life extension


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 the maximum and the average lifespan . The ability to achieve this, however, does not currently exist. [1]

Some researchers in this area, and “life extensionists”, “immortalists” or “longevists” (or who wish to achieve longer lives themselves), believe that future breakthroughs in tissue rejuvenation , stem cells , regenerative medicine , molecular repair, gene therapy , pharmaceuticals, and organ replacement (such as with artificial organs or xenotransplantations ) will eventually enable humans to have indefinite lifespans (agerasia [2] ) through complete rejuvenation to a healthy youthful condition. The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists .

The sale of purported anti-aging products such as supplements and hormone replacement is a lucrative global industry. For example, the industry That Promotes the use of hormones as a treatment for Consumers to slow or reverse the aging process in the US market generated about $ 50 trillion of revenue a year in 2009. [1] The use of Such products Has not-been proven to be effective or safe. [1] [3] [4] [5]

Average and maximum lifespan

Main article: Senescence

During the process of aging , an organism accumulates damage to its macromolecules , cells , tissues , and organs . Genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. [6] Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging. [7] [8]

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 maximum the lifespan of a wildtype mouse , Commonly used as a model in research is aging, is about three years. [9] Genetic differences between humans and mice that account for these differences in the performance of DNA repair , antioxidant defenses, energy metabolism , proteostasis maintenance, and autophagy . [10]

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. Expansion of expected lifespan can be achieved by getting medical care, vaccinations , good diet , exercise and avoidance of smoking .

Maximum lifespan is determined by the rate of aging for a species in their genes and by environmental factors. Widely recognized methods of extending maximum lifespan in such organisms as nematodes , fruit flies, and mice include caloric restriction , gene manipulation , and administration of pharmaceuticals. [11] Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality. [12] [13]Some animals such as hydra , planarian flatworms , and certain sponges , corals, and jellyfish do not die of age and exhibit potential immortality. [14] [15] [16] [17]

Strategies

See also: Ageing § Prevention and reversal

Diets and supplements

Much life extension research focuses on nutrition- diets or supplements – there is little evidence that they have an effect. The many diets promoted by anti-aging advocates are often contradictory. original research? ]

In some studies calorie restriction has been shown to extend the life of mice, yeast, and rhesus monkeys. [18] [19] However, a more recent study did not find calorie restriction to improve survival in rhesus monkeys. [20] In humans the long-term health effects of moderate caloric restriction with sufficient nutrients are unknown. [21]

The free-radical theory of aging suggests that antioxidant supplements may extend human life. However, evidence suggests that β-carotene supplements and high doses of vitamin E increase mortality rates. [22] Resveratrol is a sirtuin stimulant That has-been shown to extend life in animal models, aim the effect of resveratrol in humans is lifespan is unclear as of 2011. [23]

Hormone treatment

The anti-aging industry offers several hormone therapies . Some of these have been criticized for possible dangers and a lack of proven effect. For example, the American Medical Association has been critical of some anti-aging hormone therapies. [1]

While growth hormone (GH) decreases with age, the evidence for use of growth hormone as an anti-aging therapy is mixed and mostly based on animal studies. There are mixed reports that GH or IGF-1 modulates the aging process in humans and the outcome is positive or negative. [24]

History

The extension of life in the history of scientific pursuits and ideas throughout the history of the Sumerian Epic of Gilgamesh and the Egyptian Smith medical papyri , all the way through the Taoists , Ayurveda practitioners, alchemists , hygienists such as Luigi Cornaro , Johann Cohausen and Christoph Wilhelm Hufeland , and philosophers such as Francis Bacon , Rene Descartes , Benjamin Franklin and Nicolas Condorcet. However, the beginning of the modern period in this endeavor can be traced to the end of the 19th – beginning of the 20th century, to the so-called ” end-of-the-century ” (end of the century) period, denoted as an “end of an epoch” and characterized by the rise of scientific optimism and therapeutic activism, entailing the pursuit of life extension (or life-extensionism). The Elie Metchnikoff (1845-1916) – the author of the cell theory of immunity and vice director of Pasteur Institute in Paris, and Charles-Édouard Brown-Sequard ( 1817-1894) – the president of the French Biological Society and one of the founders of modern endocrinology. [25]

Sociologist James Hughes claims that science has been tied to a cultural narrative of conquering death since the Age of Enlightenment . He quotes Francis Bacon (1561-1626) as an advocate of using science and reason to extend human life, noting Bacon’s novel New Atlantis . Robert Boyle (1627-1691), founding member of the Royal Society , also hoped that science would make substantial progress with life extension, according to Hughes, and proposed such experiments as “to replace the blood of the aged with the blood of the young “. Biologist Alexis Carrel(1873-1944) was inspired by a belief in indefinite human life that he developed after experimenting with cells , says Hughes. [26]

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 biogenerologists that is devoted to research and 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 Life Extension bestselling book : 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 restrictionto extend the lifespan of rodents in the Delay of Aging and Disease by Dietary Restriction ( ISBN  0-398-05496-7 ). It has been known that 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 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 was launched in 1962 by Robert Ettinger’s book, The Prospect of Immortality . In the 1960s, Saul Kent had been 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 to be sure Williams had really wanted to be cryopreserved. quote needed ]

Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension Foundation. 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. [27]

In 2003, Doubleday published “The Immortal Cell: One Scientist’s Quest to Solve the Mystery of Human Aging,” by Michael D. West . West emphasized the potential role of embryonic stem cells in life extension. [28]

Other writer Gennady Stolyarov , who insists that death is “the enemy of us all, to be fought with medicine, science, and technology”; [29] transhumanist philosopher Zoltan Istvan , who proposes that the “transhumanist must be one’s own existence above all else”; [30] futurist George Dvorsky , Who considers aging to be a problem That desperately needs to be solved; [31] and recording artist Steve Aoki , who has been called “one of the most prolific campaigners for life extension”. [32]

Scientific research

In 1991, the American Academy of Anti-Aging Medicine (A4M) was formed as a non-profit organization to create an anti-aging medical specialty separate from geriatrics , and to hold trade shows for physicians interested in anti-aging medicine. . The A4M trains doctors in anti-aging medicine and the field of anti-aging research. It has about 26,000 members, of which over 97% are doctors and scientists. [33] The American Board of Medical Specialties does not have anti-aging medicine nor the A4M’s professional standing. [34]

In 2003, Aubrey de Gray and David Gobel formed the Methuselah Foundation , which gives financial grants to anti-aging research projects. In 2009, de Gray and several others founded the SENS Research Foundation , a California-based scientific research organization which conducts research into aging and other anti-aging research projects at various universities. [35] 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. [36] It is led by Arthur D. Levinson , [37]and Its research team includes scientists Such As Hal V. Barron , David Botstein , and Cynthia Kenyon . In 2014, Craig Venter’s biologist founded Human Longevity Inc., a company dedicated to scientific research and end-to-end genomics and cell therapy. They received funding with the goal of compiling a comprehensive human genotype, microbiome, and phenotype database. [38]

Aside from private initiatives, Harvard and UCLA . University researchers have made a number of breakthroughs in the lives of mice and insects by reversing certain aspects of aging. [39] [40] [41] [42]

Ethics and politics

Policies relating to the substances of life extension. quote 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. They are subject to monitoring and enforcement by the Federal Trade Commission (FTC), which claims by marketers. What constitutes the difference between truthfulness and false claims is a controversial issue in this arena. quote needed ]

Scientific controversy

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 as a result of unproven anti-aging supplements . [4]

Consumer motivations

Research by Sobh and Martin (2011) suggests that people buy anti-aging products to obtain a life-long self-esteem (eg, keeping a youthful skin) or to avoid a feared-self (eg, looking old). The research shows that when consumers pursue their expectations, they are more likely to be motivated by the product. The research also shows why doing badly when doing it. Interestingly, when it is more likely to be motivated than to be successful when it comes to seeking out a feared self. [43]

Political parties

Though Many scientists state [44] That life extension and life extension radical are possible, there are still no national or international programs Focused on life radical 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 aim to provide political support to radical life research and technologies, and to ensure the fastest possible time of the future. most currently living people. [45]

Silicon Valley

Some tech innovators and Silicon Valley entrepreneurs have been heavily involved in anti-aging research. This includes Larry Ellison (founder of Oracle ), Peter Thiel ( Paypal CEO), [46] Larry Page (co-founder of Google ), and Peter Diamandis . [47]

Commentators

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. [48] He states his opposition to life extension with the words:

“[The] desire to prolong youthfulness is not only a child’s desire to eat one’s life, but also one of life. and keep it; it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity. ” [49]

John Harris, editor-in-chief of the Journal of Medical Ethics, argues that 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. [50]

Transhumanist Philosopher Nick Bostrom has asked you to comment that you have no choice. [51] 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. [52]

Overpopulation concerns

Controversy about life extension is possible to overpopulation and possible effects on society. [53] Biogerontologist Aubrey De Gray counters the criticism by pointing out overpopulation que la Therapy Could Eliminate or postpone menopause , Allowing women to space out pregnancies Their over more years and THUS decreasing the yearly population growth rate. [54] Moreover, the philosopher and futurist Max More Argues That, Given the fact the worldwide population growth rate is Slowing down and is projected to begin falling and Stabilize Eventually, Superlongevity Would Be Unlikely to contribuer to overpopulation. [53]

Opinion polls

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% of people thought it would be more than 120 years old. The median “ideal lifespan” was 91 years of age and the majority of the public (63%) viewed 41% of Americans believed that radical life extension (RLE) would be good for society, while 51% said it would be bad for society. [55]One possibility for why 56% of Americans claim they would reject life extension may be due to the cultural perception that living longer would be a result of decrepitude, and that the elderly in our current society are unhealthy. [56]

Religious people are more likely to oppose life extension than the unaffiliated, [55] though some variation exists between religious denominations.

Aging as a disease

Most mainstream medical organizations and practitioners do not consider aging to be a disease. citation needed ] David Sinclair says: “I do not see aging as a disease, but a collection of quite predictable diseases caused by the deterioration of the body”. [57] The two main arguments are not inevitable. [58] However, not everyone agrees. Harry R. Moody, director of academic affairs for AARP , notes that what is normal [59] David Gems, Assistant Director of the Institute of Healthy Aging, strongly argues that aging should be viewed as a disease.[60] In response to the universality of aging David Gems Notes That It is as misleading as arguing That Basenji arent dogs Because They Do not bark. [61] 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. [62]

The discussion of aging should be considered as a matter of importance. It would increase pharmaceutical companies in the United States of America, it would also increase the regulation of the anti-aging market by the FDA. Anti-aging agents for the treatment of cancer. [61] [63]

Research

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 cells and tissues Deteriorated, reversal of harmful epigenetic exchange, gold enhancement of the telomerase enzyme activity. [64] [65]

Research in the field of life extension strategies in various organizations is currently under way. Since 2009, investigators have found ways to increase the survival of nematode worms and yeast by 10-fold; The record in nematodes was achieved through genetic engineering and the extension in a combination of genetic engineering and caloric restriction . [66]A 2009 review of longevity research noted: “Longevity gains from dietary restriction, or from mutations studied previously, yield smaller benefits to Longevity gains from dietary restriction Drosophila than to nematodes, and smaller still to mammals., Lifespring, and mammals, and humans living near the world. their ancestors have already undergone several hundred million years of natural selection favoring traits that could directly or indirectly have increased the likelihood oflife-extension factor “that could apply across taxa presumed to linear response rarely seen in biology.”[66]

Anti-aging drugs

There are a number of chemicals intended for the slow aging process currently being studied in animal models . [67] One kind of research is related to the Observed effects of a calorie restricted (CR) diet, qui has-been shown to extend lifespan In Some animals [68] Based On That research, there-have-been Attempts to Develop drugs That will-have le même effect on the aging process as a caloric restriction diet, are qui Known as Caloric restriction mimetic drugs. Some drugs that are already approved for other uses have been studied for possible longevity effects on laboratory animals because of a possible CR-mimic effect; they include rapamycin , [69] metformin and other geroprotectors . [70] MitoQ , resveratrol and pterostilbene are dietary supplements that have been studied in this context. [71] [72] [73]

Other attempts to create anti-aging drugs have taken different research paths. One notable direction of research into the possibility of using the enzyme telomerase in the process of telomere shortening . [74] However, there are potential dangers in this, because some telomerase to cancer and to tumor growth and formation. [75]

Nanotechnology

Future advances in nanomedicine could lead to life in the future . 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 Nanomedicines could completely remedy the effects of aging by 2030.[76] According to Richard Feynman , it was his graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of ​​a medical use for Feynman’snanomachines (see biological machine ). Hibbs suggested that some machines might be reduced in size to the point that they would, in theory, be possible to (as Feynman put it) ” swallow the doctor “. The idea was incorporated into Feynman’s 1959 essay The Plenty of Room at the Bottom . [77]

Cloning and body part replacement

Some life extensionists That suggest therapeutic cloning and stem cell research one day Could Provide a way to generate cells, body parts, or Even Entire bodies (Generally Referred to as reproductive cloning ) That Would Be genetically identiques to a prospective patient. Recently, the US Department of Defense initiated a program to research the possibility of growing human body parts on mice. [78] Complex biological structures, such as mammalian joints and limbs, have not yet been replicated. Dog and primate brain transplant experiments Were Conducted in the mid-20th century goal failed due to rejectionand the inability to restore nerve connections. As of 2006, the implantation of bio-engineered bladders grew from patients’ own cells to a viable treatment for bladder disease. [79] Proponents of body part replacement and cloning contend that the biotechnologies are likely to be more than other life-extension technologies.

The use of human stem cells , particularly embryonic stem cells , is controversial. Opponents’ objections are based on interpretations of religious teachings or ethical considerations. Proponents of stem cell research, which are routinely formed and destroyed in a variety of contexts. Use of stem cells from the umbilical cord can not provoke controversy. [80]

The controversies over cloning are similar, general public opinion except 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 to diseases) This is the goal of the 2045 Initiative . [81]

Cryonics

Main article: Cryonics

For cryonics (advocates of cryopreservation ), staging the body at low temperatures after death can provide an “ambulance” into a future in which advanced medical technologies may allow resuscitation and repair. They speculate cryogenic temperatures will be reduced to large enough in the tissues of the body, and they will be able to reduce the burden of the disease by the cryopreservation process.

Many do not believe cryonicists 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 can 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. [82]Cryonicists who? ] state that rapid cooling and cardio- pulmonary carrier applied time immediately after-certification 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 submersion in ice water. In one case, full recovery was reported after 45 minutes underwater. [83] To facilitate the rapid preservation of cells and tissues, cryonics “standby teams” are available to wait for the patients who are at the cryopreserved to apply for cooling and cardio-pulmonary support as soon as possible after the declaration of death. [84]

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 future capabilities . [85] [86]

Strategies for Engineered Negligible Senescence (SENS)

Main articles: Strategies for Engineered Negligible Senescence and Genetics of Aging

Another proposed life extension technology would combine existing and predicted future biochemical and genetic techniques. SENS proposes that rejuvenation may be achieved by the use of stem cells and tissue engineering , telomere- lengthening machinery, allotopic expression of mitochondrial proteins, targeted ablation of cells, immunotherapeutic clearance, and novel lysosomal hydrolases . [87]

While many biogenerologists find these ideas “worthy of discussion” [88] [89] and SENS conferences feature important research in the field, [90] [91] some contend that the alleged benefits are too speculative of the current state of technology to it as “fantasy rather than science”. [3] [5]

Genetic modification

Gene therapy , in qui nucleic acid polymers are Delivered as a drug and are Either Expressed as proteins, interferes with the Expression of proteins, proper or genetic mutations, has-beens Proposed as a future strategy to prevent prevention aging. [92] [93]

A large array of genetic modifications 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. [94]

Fooling genes

In The Selfish Gene , Richard Dawkins describes an approach to life-extension that involves “fooling genes” into thinking the body is young. [95] Dawkins attributes inspiration for this idea to Peter Medawar. The basic idea is that our bodies are made up of our genes, we are older when we are older. Presumably, these genes are activated by these factors and can be induced by these genes. It is a statistic that we have more lethal genes that activate in life than in early life. Therefore, to extend life, we should be able to prevent these phenomena from occurring, and we should be able to do so by “identifying changes in the internal chemical environment”. superficial chemical properties of a young body “. [96]

Reversal of informational entropy

According to some lines of thinking, [97] and thus loss of information. In this article, gerontologist Marios Kyriazis suggests that it is necessary to increase the input of actionable and meaningful information both individually (into individual brains), [98] and collectively (into societal systems). [99] 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 can lead to a reduction of death rate, ie indefinite lifespan . [100]

Mind uploading

Main article: Mind uploading

One hypothetical future strategy that, as some suggest, who? ] “eliminates” the complications related to a physical body, involves the copying or transferring (eg 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 analyze the structure of a particular brain, and then to build a software that is so faithful to the original that . [101]Whether or not an exact copy of one’s mind is actual life extension is matter of debate.

Some scientists believe that the dead may be “resurrected” through simulation technology. [102]

Young blood injection

Some clinics currently offering injection of blood products from young donors. The alleged benefits of the treatment, include a better life, darker hair, better memory, better sleep, heart disease cure, diabetes and Alzheimer. [103] [104] [105] [106] [107] The approach is based on parabiosis studies neurologists such as Irina Conboy do on mice, but Conboy says young blood does not reverse aging (even in mice) and that those who offer those treatments have misunderstood her research. [104] [105]Neuroscientist Tony Wyss-Coray, who also commented on blood exchanges on the subject as of 2014, said people offering those treatments are “basically abusing people’s trust” [108] [105] and that young blood treatments are “the scientific equivalent of fake news” . [109] The treatment appeared in HBO’s Silicon Valley fiction series. [108]

Two clinics in California, run by Jesse Karmazin and David C. Wright, [103] offer $ 8,000 injections of plasma from the blood of young people. Karmazin has not published in any peer-reviewed journal and does not use a control group. [109] [108] [103] [105]

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