those that scientists think may be pertinent
or maximum lifespan. These findings suggest
to calorie restriction. The most relevant are
that resveratrol does not affect all aspects of
the sirtuins and mTOR (mammalian target
the basic aging process and that there may
of rapamycin) pathways as discussed on
be different mechanisms for health versus
page 16. In several, but not all cases, disrupting
lifespan. Research on resveratrol continues
these pathways means the organism no lon-
in mice, along with studies in nonhuman
ger responds positively to calorie restriction.
primates and people.
These two pathways have been important
Rapamycin, another possible calorie
for identifying at least two compounds that
restriction mimetic, acts on the mTOR path-
may mimic the effects of calorie restriction:
way. This compound’s main clinical use is to
resveratrol and rapamycin.
help suppress the immune system of people
Resveratrol, found naturally in grapes,
who have had an organ transplant so that
wine, and nuts, activates the sirtuin pathway.
the transplant can succeed. A study by NIA’s
It has been shown to increase the lifespan
Interventions Testing Program, as discussed
of yeast, flies, worms, and fish. In 2006, NIA
on page 7, reported in 2009 that rapamycin
researchers, in collaboration with university
extended the median and maximum lifespan
scientists funded by NIA, reported on a study
of mice, likely by inhibiting the mTOR path-
comparing mice fed a standard diet, a high
way. Rapamycin had these positive effects
fat-and-calorie diet, or a high fat-and-calorie
even when fed to the mice beginning at
diet supplemented with resveratrol beginning early-old age (20 months), suggesting that at middle age. Resveratrol appeared to lessen
an intervention started later in life may still
the negative effects of the high fat-and-calorie be able to increase longevity. Researchers are diet, both in terms of lifespan and disease. In
now looking at rapamycin’s effects on health
a 2008 follow-up study, investigators found
span and if there are other compounds that
that resveratrol improved the health of aging
may have similar effects as rapamycin on
mice fed a standard diet. It prevented age- and the mTOR pathway.
obesity-related decline in heart function.
Scientists do not yet know how resveratrol,
Mice on resveratrol had better bone health,
rapamycin, and other compounds that dem-
reduced cataract formation, and enhanced
onstrate effects similar to calorie restriction
balance and motor coordination compared to
will influence human aging. Learning more
non-treated mice. In addition, resveratrol was
about these calorie restriction mimetics, and
found to partially mimic the effects of calorie
the mechanisms and pathways underlying
restriction on gene expression profiles of
liver, skeletal muscle, and adipose (fatty) tissue
calorie restriction, may point the way to future
in the mice. However, the compound did not
healthy aging therapies.
have an impact on the mice’s overall survival
BIOLOGY OF AGING: RESEARCH TODAY FOR A HEALTHIER TOMORROW 29
30
IMMUNE
SYSTEM