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Old age may be relative, with some organisms
living only a few hours and others surviving for decades,
but research just released suggests that the processes responsible
for aging may be similar in a wide variety of living things.
The so-called insulin-signaling pathway,
already known to regulate aging in worms, appears to play
a similar role in fruit flies and yeast.
The findings suggest that the pathway
helps regulate the aging process throughout the animal kingdom,
according to scientists involved in the research.
These findings suggest that there
is a genetic system common to all animals that regulates aging.
If we could just tap into the mammalian
version of that system it might be possible to retard
or even reverse human aging -- at least in principle.
Scientists have known that a gene involved
with the sugar-processing hormone insulin and a related substance,
insulin-like growth factor (IGF), affect the lifespan of a
type of roundworm called C. elegans. Mutations in a gene called
daf-2 dramatically
increase the worms' lifespan.
Investigators report that they have extended
the lifespans of fruit flies by mutating a gene involved in
the insulin-IGF pathway. Flies with the variant form of this
gene, known as chico, lived nearly 50%
longer than other flies.
The long-living flies were smaller
than average, probably due to decreased IGF levels.
In mammals, including people, IGF levels tend to be linked
to size -- bigger animals have higher levels of the growth
factor.
But fruit flies do not have to sacrifice
size for longevity, according to the report. The investigators
found that flies with only one defective copy of the chico
gene also lived longer than normal flies, but were not dwarfs.
Since research has suggested that reproduction
can shorten lifespan, the researchers
tested whether the life-extending effects of the chico variation
depended on a fly being sterile.
Most of the flies with two mutated copies
of chico were sterile.
Investigators tinkered with the genes
of another set of fruit flies to make them sterile. Compared
to this group of flies, the flies with the mutated versions
of chico still lived longer, suggesting that something
besides fertility must affect longevity.
Tatar's team achieved similar results
when they bred a strain of fruit flies with a mutant version
of a gene in the insulin-signaling pathway called InR, which
corresponds to the lifespan regulating daf-2 gene in worms.
The resulting female fruit flies were smaller than normal,
but they lived 85% longer
than the average fruit fly. Male flies were also smaller,
but many of them died early in life. Males that survived,
however, did tend to live longer than normal male fruit flies.
Since InR's normal function includes signaling
the release of a hormone called juvenile hormone, the researchers
treated the mutant flies with the hormone to see what effect
it would have on lifespan. Flies treated with the hormone
had lifespans that were more in line with normal fruit flies,
the report indicates.
The results
suggest that hormones may eventually be used to alter the
aging process in people.
Science April
6, 2001;292:104-110
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