Will Human Aging Be Postponed?

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In theory, it certainly can.Yet no single elixir will do the trick. Antiaging therapies of the
future will undoubtedly have to countermany destructive biochemical processes at once

Aging remains inevitable, but scientists now have a strategy in place for figuring out
how to retard the process.
Cultures throughout history have aspired to postpone aging, thereby prolonging vitality and life itself.
Today macrobiotic diets, recycled Hindu health practices, the latest fashions in gray-market hormone
therapy and other forms of chicanery continue to fan the flames of hope. All these attempts to restore or
sustain youthful vigor have just one thing in common: failure to achieve their goal. People who survive
past 65 these days are only slightly more likely to enjoy a robust old age than their counterparts were
2,000 years ago. Medical researchers have devised useful therapies for disorders that become more
common with advancing age, such as cancer and heart disease. And over the past 120 years, sanitation
systems and drugs that combat infectious disease have increased life expectancy in the developed nations
by reducing premature death. But nothing delays or slows the innate processes that cause adults to age, to
suffer a decline in physiological functioning as they grow older.

Discovery by evolutionary biologists explains why we age. Calculations show that the force of
natural selection on survival in sexually reproducing populations drops soon after the earliest age
of reproduction is reached. Aging has evolved because genes that produce deleterious effects late in
life meet little or no opposition from natural selection and thus become rampant in the gene pool.

Consequently, successful treatment of one illness late in life often means that another age-related
problem soon takes its place. Infirmity remains the lot of those older than 80, however much the media
may dote on the 90-year-old marathon runner. None of this means that postponing aging will be
impossible forever. Since 1980 many studies have achieved that feat in animals, albeit by methods that
cannot be applied to humans. The situation of aging research in 1999 is thus like that of atomic physics in
1929. Physicists by then had discovered previously unimagined quantum forces. The question was, Could
they harness those forces? Aging research has made great progress recently, but has it advanced enough
to defer our years of infirmity?
Not yet. To meet that goal, investigators need a much better understanding of the physiological
processes that underlie senescence and influence life span. I am, however, optimistic that these processes
can be discerned, because a more fundamental mystery has been solved: Why has aging evolved in the
first place? The answer has enabled researchers to develop a rational strategy for unearthing the
biochemical pathways that might bemanipulated to extend our years of vigor.

Natural Selection Snoozes

Aging does not occur because of some universal defect in all cell types. If some singular,
unavoidable flaw caused every cell to fail eventually, no animal would escape aging. But some do. For
example, asexual sea anemones kept for decades in aquariums do not show failing health. Nor does aging
derive from a genetic program designed by nature to block overpopulation. Instead senescence is the by-
product of a pattern of natural selection that afflicts humans and other vertebrates but not vegetative sea
anemones. More specifically, aging arises in sexually reproducing species because the force of natural
selection declines after the start of adulthood.
This concept follows logically from general evolutionary theory. Heritable traits persist and
become prevalent in a population—they are selected, in evolutionary terms—if those properties help their
bearers to survive into reproductive age and produce offspring. The most useful traits result in the most
offspring and hence in the greatest perpetuation of the genes controlling those properties. Meanwhile
traits that diminish survival in youth become uncommon—are selected against—because their possessors
often die before reproducing.
In contrast to deleterious genes that act early, those that sap vitality in later years would be
expected to accumulate readily in a population, because parents with those genes will pass them to the
next generation before their bad effects interfere with reproduction. (The later the genes lead to disability,
the more they will spread, because the possessors will be able to reproduce longer.) Aging, then, creeps
into populations because natural selection, the watchdog that so strongly protects traits ensuring hardiness
during youth, itself becomes increasingly feeble with adult age. Two devastating genetic
diseases dramatize this point. Progeria, caused by a chance mutation in one copy of one gene in a new
embryo, leads to nightmarish deterioration during childhood. Many systems degenerate so quickly that
the youngsters soon come to look as old as their grandparents. They commonly die of heart disease or
stroke before their 15th birthday. Huntington’s disease, which is also caused by a defect in one copy of a
gene, manifests itself in middle age. In this case, the nervous system degenerates, eventually leading to
death.
Progeria is rare, whereas Huntington’s is relatively common among genetic disorders. Why?
People with progeria die before reproducing. In this way, intense natural selection readily removes the
progeria mutation from the gene pool whenever it arises. The mutation for Huntington’s, on the other
hand, does not interfere significantly with reproduction, because it does not yield disability until after
people have produced all or most of their children. It manifests at a stage when the force of natural
selection is weak.
In the 1940s and 1950s J.B.S. Haldane and Nobelist Peter B. Medawar, both at University College
London, were the first to introduce this evolutionary explanation of aging. W. D. Hamilton of Imperial
College and Brian Charlesworth of the University of Sussex then made the thesis mathematically rigorous
in the 1960s and 1970s.
In their most important result, Hamilton and Charlesworth established that for organisms that do
not reproduce by splitting in two, the force of natural selection on survival falls with adult age and then
disappears entirely late in life. Because natural selection is the source of all adaptation, and thus of health,
the hardiness of older organisms declines as natural selection fades out. Eventually, with the continued
absence of natural selection at later ages, survival may be so imperiled that optimal conditions and
medical care may be unable to keep the older individual alive.
Since the 1970s the original mathematical proofs have been confirmed experimentally many
times, most often by manipulations that deliberately prolong the period of intense natural selection in
laboratory animals. Investigators extend this period by delaying the age at which reproduction begins;
they discard all fertilized eggs produced by young animals and use only those produced late in life. As a
result, only individuals who are robust enough to reproduce at an advanced age will pass their genes to
the next generation.
If the declining strength of natural selection after the start of reproduction really does explain the
evolution of aging, then progressively retarding this drop for a number of generations in a test population
should lead to the evolution of significantly postponed aging in that lineage. This prediction has been
shown to be true in fruit flies of the genus Drosophila that have had reproduction delayed across 10 or
more generations. As a result of these experiments, scientists now have stocks that live two to three times
longer than normal and are healthy longer as well. The flies that display postponed aging are surprisingly
perky. They do not merely sustain normal biological functions for longer periods; they display superior
capabilities at all adult ages. In youth and later, they are better able to resist such normally lethal stresses
as acute desiccation and starvation. They also show more athletic prowess than their like-aged
counterparts do, being able
to walk and fly for longer periods.
If people could be treated in the same way as fruit flies, the problem of postponing human aging
could be solved by forcibly delaying childbirthover many generations. Such practices would be barbaric,
however, as well as extremely slow in producing results. Those who wish to delay aging must therefore
find other methods, ones that would essentially mimic the physiological changes brought about by
generations of postponed breeding. (A note to those who are tempted to try postponing breeding: the
practice will not yield any immediate benefit to you or your future children. It would probably take about
10 generations to increase longevity at all and centuries to yield a significant increase in life span.)