Most longevity genes identified thus far influence one of
three pathways in a cel : insulin/IGF-1, sirtuins, or mTOR.
In the 1980s, scientists discovered the first gene
a role in human aging. These genes may be
shown to limit lifespan in roundworms, which they named
important to future development of thera-
age-1. Further investigation revealed that the effects of pies to support healthy aging.
age-1 are involved with the insulin/IGF-1 pathway. When Another approach, the genome-wide
scientists “silenced” the age-1 gene’s activity, the insulin/
association study, or GWAS, is particularly
IGF-1 pathway’s activity also decreased and the worms
productive in finding genes involved in
lived longer. Since then, many other genes associated
diseases and conditions associated with
with the insulin/IGF-1 pathway have been found to
aging. In this approach, scientists scan
affect the lifespan of fruit flies and mice, strengthening
the entire genome looking for variants
the hypothesis that the insulin/IGF-1 pathway plays an
that occur more often among a group
important role in the aging process. More research is
with a particular health issue or trait. In
needed to determine if inhibiting this pathway could
one GWAS study, NIH-funded researchers
increase longevity in humans or create insulin-related
identified genes possibly associated with
health problems like diabetes. A recent report suggests that
high and low blood fat levels, cholesterol,
people with a mutation related to the insulin/IGF-1 pathway
and, therefore, risk for coronary artery
may have less risk of developing diabetes and cancer.
disease. The data analyzed were collected
There is also a great deal of interest in the sirtuin
from Sardinians, a small genetically alike
pathway. Sirtuin genes are present in al species and
population living off the coast of Italy in
the Mediterranean, and from two other
regulate metabolism in the cel . They are crucial for
international studies. The findings
cel activity and cel life. In the 1990s, scientists at the
revealed more than 25 genetic variants
Massachusetts Institute of Technology found that
in 18 genes connected to cholesterol and
inserting an extra copy of a sirtuin equivalent, cal ed Sir2, lipid levels. Seven of the genes were not
increased the lifespan of yeast. Extension of lifespan has
previously connected to cholesterol/lipid
been replicated in other organisms, including flies and worms.
levels, suggesting that there are possibly
However, studies in mice have yielded conflicting results.
other pathways associated with risk for
The mTOR pathway—an abbreviation of “mammalian
coronary artery disease. Heart disease is
target of rapamycin”—plays a role in aging of yeast,
a major health issue facing older people.
worms, flies, and mice. This pathway controls the cel ’s
Finding a way to eliminate or lower risk
rate of protein synthesis, which is important for proper cell
for heart disease could have important
function. Researchers have found that inhibiting the pathway
ramifications for reducing disability
in mice genetical y or pharmacological y (using rapamycin)
and death from this particular age-
leads to increased longevity and improved health span.
related condition.
Scientists are also currently using
GWAS to find genes directly associated
with aging and longevity. Because the
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GENETICS
THE FUTURE OF AGING RESEARCH