Life extension

Life extension is the concept of extending the human lifespan, either modestly – through improvements in medicine – or dramatically by increasing the maximum lifespan beyond its generally settled limit of 125 years.[1] The technology to achieve such dramatic changes, however, does not currently exist.[2]

For other uses, see Life extension (disambiguation).

Several researchers in this area, along with "life extensionists", "immortalists" or "longevists" (those who wish to achieve longer lives themselves), postulate 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[3]) 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 billion of revenue a year in 2009.[2] The use of such products however has not been proven to be effective or safe.[2][4][5][6]

Average and maximum lifespan
Main article: Senescence

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."[7] Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well.[8][9]

The longest documented human lifespan is 122 years, the case of Jeanne Calment who according to records 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.[10] 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.[11]

The 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.[12] Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality.[13][14] Some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.[15][16][17][18]

Strategies
See also: Ageing § Prevention and delay

Diets and supplements

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

In some studies calorie restriction has been shown to extend the life of mice, yeast, and rhesus monkeys.[19][20] However, a more recent study did not find calorie restriction to improve survival in rhesus monkeys.[21] In humans the long-term health effects of moderate caloric restriction with sufficient nutrients are unknown.[22]

The free-radical theory of aging suggests that antioxidant supplements might extend human life. Reviews, however, have found that vitamin A (as β-carotene) and vitamin E supplements may increase mortality.[23][24] Other reviews have found no relationship between vitamin E and other vitamins with mortality.[25]

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.[2]

While growth hormone (GH) decreases with age, the evidence for use of growth hormone as an anti-aging therapy is mixed and based mostly on animal studies. There are mixed reports that GH or IGF-1 modulates the aging process in humans and about whether the direction of its effect is positive or negative.[26]

History

The extension of life has been a desire of humanity and a mainstay motif in the history of scientific pursuits and ideas throughout history, from the Sumerian Epic of Gilgamesh and the Egyptian Smith medical papyrus, 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, René 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 "fin-de-siècle" (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). Among the foremost researchers of life extension at this period were the Nobel Prize winning biologist Elie Metchnikoff (1845-1916) -- the author of the cell theory of immunity and vice director of Institut Pasteur in Paris, and Charles-Édouard Brown-Séquard (1817-1894) -- the president of the French Biological Society and one of the founders of modern endocrinology.[27]

Sociologist James Hughes claims that science has been tied to a cultural narrative of conquering death since the Age of Enlightenment. He cites Francis Bacon (1561–1626) as an advocate of using science and reason to extend human life, noting Bacon's novel New Atlantis, wherein scientists worked toward delaying aging and prolonging life. 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 old with the blood of the young". Biologist Alexis Carrel (1873–1944) was inspired by a belief in indefinite human lifespan that he developed after experimenting with cells, says Hughes.[28]

Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension organization included seizure of merchandise and court action.[29] In 1991, Saul Kent and Bill Faloon, the principals of the organization, were jailed for four hours and were released on $850,000 bond each.[30] After 11 years of legal battles, Kent and Faloon convinced the US Attorney's Office to dismiss all criminal indictments brought against them by the FDA.[31]

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.[32]

Other modern life extensionists include writer Gennady Stolyarov, who insists that death is "the enemy of us all, to be fought with medicine, science, and technology";[33] transhumanist philosopher Zoltan Istvan, who proposes that the "transhumanist must safeguard one's own existence above all else";[34] futurist George Dvorsky, who considers aging to be a problem that desperately needs to be solved;[35] and recording artist Steve Aoki, who has been called "one of the most prolific campaigners for life extension".[36]

Scientific research

In 1991, the American Academy of Anti-Aging Medicine (A4M) was formed. The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing.[37]

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.[38] 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.[39] It is led by Arthur D. Levinson,[40] 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. They received funding with the goal of compiling a comprehensive human genotype, microbiome, and phenotype database.[41]

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.[42][43][44][45]

Ethics and politics

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 in response to what they see as unscrupulous profiteering from the sale of unproven anti-aging supplements.[5]

Consumer motivations

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. When product use is seen to fail it is more motivating than success when consumers seek to avoid a feared-self.[46]

Political parties

Though many scientists state[47] 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.[48]

Silicon Valley

Some tech innovators and Silicon Valley entrepreneurs have invested heavily into anti-aging research. This includes Larry Ellison (founder of Oracle), Peter Thiel (former PayPal CEO),[49] Larry Page (co-founder of Google), and Peter Diamandis.[50]

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.[51] 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."[52]

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.[53]

Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few.[54] 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.[55]

Overpopulation concerns

Controversy about life extension is due to fear of overpopulation and possible effects on society.[56] 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.[57] 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.[56]

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% 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 (RLE) would be good for society, while 51% said they believed it would be bad for society.[58] 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.[59]

Religious people are no more likely to oppose life extension than the unaffiliated,[58] though some variation exists between religious denominations.

Aging as a disease

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".[60] The two main arguments used are that aging is both inevitable and universal while diseases are not.[61] However, not everyone agrees. Harry R. Moody, director of academic affairs for AARP, notes that what is normal and what is disease strongly depend on a historical context.[62] David Gems, assistant director of the Institute of Healthy Ageing, argues that aging should be viewed as a disease.[63] 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.[64] 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.[65]

The discussion whether aging should be viewed as a disease or not has important implications. One view is, this 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.[64][66]

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 deteriorated cells and tissues, reversal of harmful epigenetic changes, or the enhancement of enzyme telomerase activity.[67][68]

Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions. Since 2009, investigators have found 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.[69] 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."[69]

Anti-aging drugs

There are a number of chemicals intended to slow the aging process currently being studied in animal models.[70] One type of research is related to the observed effects of a calorie restriction (CR) diet, which has been shown to extend lifespan in some animals.[71] 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. 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,[72] metformin and other geroprotectors.[73] Coenzyme Q, resveratrol and pterostilbene are dietary supplements that have also been studied in this context.[74][75][76]

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.[77] However, there are potential dangers in this, since some research has also linked telomerase to cancer and to tumor growth and formation.[78]

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.[79] According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman's theoretical nanomachines (see biological machine). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.[80]

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.[81] 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.[82] 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.[83]

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
Main article: Cyborg

Replacement of biological (susceptible to diseases) organs with mechanical ones could extend life. This is the goal of the 2045 Initiative.[84]

Cryonics
Main article: Cryonics

Cryonics is the low-temperature freezing (usually at −196 °C or −320.8 °F or 77.1 K) of a human corpse, with the hope that resuscitation may be possible in the future.[85][86] It is regarded with skepticism within the mainstream scientific community and has been characterized as quackery.[87]

Strategies for engineered negligible senescence
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 obtained by removing aging damage via 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.[88]

While many biogerontologists find these ideas "worthy of discussion"[89][90] and SENS conferences feature important research in the field,[91][92] some contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science".[4][6]

Genetic editing
Main article: Genome editing

Genome editing, 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.[93][94]

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 50% in mice and 10-fold in nematode worms.[95]

Fooling genes

In The Selfish Gene, Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young.[96] 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".[97]

Mind uploading
Main article: 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.[98] Whether or not an exact copy of one's mind constitutes actual life extension is matter of debate.

However, critics argue that the uploaded mind would simply be a clone and not a true continuation of a person's consciousness.[99]

Some scientists believe that the dead may one day be "resurrected" through simulation technology.[100]

Young blood injection
Further information: Young blood transfusion

Some clinics currently offer injection of blood products from young donors. The alleged benefits of the treatment, none of which have been demonstrated in a proper study, include a longer life, darker hair, better memory, better sleep, curing heart diseases, diabetes and Alzheimer.[101][102][103][104][105] The approach is based on parabiosis studies 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.[102][103] Neuroscientist Tony Wyss-Coray, who also studied blood exchanges on mice as recently as 2014, said people offering those treatments are "basically abusing people's trust"[106][103] and that young blood treatments are "the scientific equivalent of fake news".[107] The treatment appeared in HBO's Silicon Valley fiction series.[106]

Two clinics in California, run by Jesse Karmazin and David C. Wright,[101] offer $8,000 injections of plasma extracted from the blood of young people. Karmazin has not published in any peer-reviewed journal and his current study does not use a control group.[107][106][101][103]

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See also

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