Life extension is the idea 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.
The ability to achieve such dramatic changes,
however, does not currently exist.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,
gene therapy, pharmaceuticals, 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 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.
The use of such products has not been proven
to be effective or safe.
== Average and maximum lifespan ==
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."
Oxidation damage to cellular contents caused
by free radicals is believed to contribute
to aging as well.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.
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.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.
Another technique uses evolutionary pressures
such as breeding from only older members or
altering levels of extrinsic mortality.
Some animals such as hydra, planarian flatworms,
and certain sponges, corals, and jellyfish
do not die of old age and exhibit potential
immortality.
== Strategies ==
=== 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.
However, a more recent study did not find
calorie restriction to improve survival in
rhesus monkeys.
In humans the long-term health effects of
moderate caloric restriction with sufficient
nutrients are unknown.The free-radical theory
of aging suggests that antioxidant supplements
might extend human life.
However, evidence suggest that β-carotene
supplements and high doses of vitamin E increase
mortality rates.
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.
=== 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.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.
== 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.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.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".
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 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.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"; transhumanist philosopher
Zoltan Istvan, who proposes that the "transhumanist
must safeguard one's own existence above all
else"; futurist George Dvorsky, who considers
aging to be a problem that desperately needs
to be solved; and recording artist Steve Aoki,
who has been called "one of the most prolific
campaigners for life extension".
=== 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.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.
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.
It is led by Arthur D. Levinson, 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.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.
== Ethics and politics ==
Politics relevant to the substances of life
extension pertain mostly to communications
and availability.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.
=== 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.
=== 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.
=== Political parties ===
Though many scientists state 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.
=== 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), Larry Page
(co-founder of Google), and Peter Diamandis.
=== 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.
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."
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.
=== Overpopulation concerns ===
Controversy about life extension is due to
fear of overpopulation and possible effects
on society.
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.
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.
=== 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.
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.Religious people
are no more likely to oppose life extension
than the unaffiliated, 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".
The two main arguments used 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 depend on a historical
context.
David Gems, assistant director of the Institute
of Healthy Ageing, 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.
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.
== 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.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.
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."
=== 
Anti-aging drugs ===
There are a number of chemicals intended to
slow the aging process currently being studied
in animal models.
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.
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,
metformin and other geroprotectors.
MitoQ, resveratrol and pterostilbene are dietary
supplements that have also been studied in
this context.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.
However, there are potential dangers in this,
since some research has also linked telomerase
to cancer and to tumor growth and formation.
=== 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.
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.
=== 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.
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.
=== Cyborgs ===
Replacement of biological (susceptible to
diseases) organs with mechanical ones could
extend life.
This is the goal of the 2045 Initiative.
=== 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.
Cryonicistsstate 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, 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.
=== Strategies for engineered negligible senescence
===
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.While
many biogerontologists find these ideas "worthy
of discussion" and SENS conferences feature
important research in the field, some contend
that the alleged benefits are too speculative
given the current state of technology, referring
to it as "fantasy rather than science".
=== Genetic 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.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.
=== Fooling genes ===
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".
=== 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.
Whether or not an exact copy of one's mind
constitutes actual life extension is matter
of debate.
Some scientists believe that the dead may
one day be "resurrected" through simulation
technology.
=== Young blood injection ===
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.
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.
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" and that
young blood treatments are "the scientific
equivalent of fake news".
The treatment appeared in HBO's Silicon Valley
fiction series.Two clinics in California,
run by Jesse Karmazin and David C. Wright,
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.
== See also
