Life Extension

Life extension science, also known as anti-aging medicine and experimental 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’ or ‘longevists’ (those who wish to achieve longer lives themselves), believe that future breakthroughs in tissue rejuvenation with stem cells, molecular repair, and organ replacement (such as with artificial organs or xenotransplantations) will eventually enable humans to have indefinite lifespans (agerasia) 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. Medical experts state that the use of such products has not been shown to affect the aging process, and many claims of anti-aging medicine advocates have been roundly criticized by medical experts, including the American Medical Association.

However, it has not been shown that the goal of indefinite human lifespans itself is necessarily unfeasible; some animals such as lobsters and certain jellyfish do not die of old age, and an award was offered to anyone who could prove life extensionist Aubrey de Grey’s hopes were ‘unworthy of learned debate’; MIT’s ‘Technology Review’ judged the contest;nobody won the prize. Bioethicists question the ethical ramifications of life extension.

During the process of aging, an organism accumulates damage to macromolecules, its cells, its tissues and its organs. This accumulated damage is the result of oxidation damage to the cell contents caused by free radicals (atoms with an unpaired electron), though other things cause aging as well. 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 mouse, commonly used as a model in research on aging, is about four years. Genetic differences between humans and mice that may account for these different aging rates include efficiency of DNA repair, types and quantities of antioxidant (atoms that donate an electron to neutralize a free radical) enzymes, and different rates of free radical production. The most important and challenging factor remains the telomere limitation of each individual species. Telomeres are a region of DNA at the end of a chromosome. They protect the ends of chromosomes from deteriorating or fusing with other chromosomes. Restoring telomeres would protect the ends of DNA from being cut off after successive divisions since each one normally removes some which is at first the telomere.

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. One widely recognized method of extending maximum lifespan in organisms such as roundworms is calorie restriction. Another technique used evolutionary pressure such as breeding from only older members. Theoretically, extension of maximum lifespan could be achieved by reducing the rate of aging damage, by periodic replacement of damaged tissues, or by molecular repair or rejuvenation of deteriorated cells and tissues and the enhancement of telomerase enzyme activity. Future research will be geared towards telomere repair strategies.

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. A dietary pattern with some support from scientific research is caloric restriction. The free-radical theory of aging suggests that antioxidant supplements, such as Vitamin C, Vitamin E, CoQ10, 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. Other substances proposed to extend lifespan include oxytocin, insulin, human chorionic gonadotropin (hCG), and erythropoietin (EPO). Resveratrol is a sirtuin stimulant that appears to extend lifespan in simple organisms such as roundworms and short-lived fish.

Some supplements, including the minerals selenium or zinc have been reported to extend the lifespan of rats and mice, though none have been proven to do so in humans, and significant toxic effects were observed. Metformin (an antidiabetic drug) may also extend life span in mice. 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.’ Ayurveda, the traditional Indian system of medicine, describes a class of longevity herbs called rasayanas. Along with their Chinese counterparts (called superior or tonic herbs), Indian rasayanas demonstrate preliminary positive results in animal models.

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. Even if 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. 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. 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. Furthermore, mouse models lacking the insulin-like growth factor also live especially long and have low levels of growth hormone.

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 theorized that this mutation may hold a key to life extension. Dr. 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,’ Dr. Longo said. He said he was not taking the drug, called pegvisomant or Somavert, which is very hard to obtain.

Some critics dispute the portrayal of aging as a disease. For example, Leonard Hayflick, who determined that fibroblasts (critical in would healing) 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. 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.

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.

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. 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. 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. 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.

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.

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. 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. No mammal has been successfully cryopreserved and brought back to life, and resuscitation from cryonics is not possible with current science. Some scientists still support the idea based on their expectations of the capabilities of future science.

Another proposed life extension technology would combine existing and predicted future biochemical and genetic techniques. SENS (Strategies for Engineered Negligible Senescence) 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. There is no scientific evidence that supports this strategy, and British molecular biologist Robin Holliday called SENS ‘overly ambitious.’

In ‘The Selfish Gene,’ Richard Dawkins describes an approach to life-extension that involves ‘fooling genes’ into thinking the body is young. 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.’

According to some lines of thinking, the ageing process is routed into a basic reduction of biological complexity, 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), and collectively (into societal systems). 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.

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,’ 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’ 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’ 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.’ It had been known since the work of Clive McCay in the 1930s that calorie restriction can extend the maximum lifespan of rodents. But it was the work of Walford and Weindruch that gave detailed scientific grounding to that knowledge. Walford’s personal interest in life extension motivated his scientific work and he practiced calorie restriction himself. Walford died at the age of 80 from complications caused by ALS (Lou Gehrig’s disease). 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. In 1992, the American Academy of Anti-Aging Medicine (A4M) was formed to create what it considered an anti-aging medical specialty distinct from geriatrics, and to hold trade shows for physicians interested in anti-aging medicine. The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M’s professional standing.

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. He stated: ‘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.’ 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.

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

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.’ The two main arguments proffered are that aging is both inevitable and universal while diseases are not. 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. David Gems, Assistant Director of the Institute of Healthy Ageing, strongly argues that aging should be viewed as a disease. 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. 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.

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.

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