In an article published early online on January 21, 2009 in the
Proceedings of the National Academy of Sciences, researchers from
Brown University in Rhode Island, the University of Chicago, and the
University of Connecticut Health Center report that a mutation that
extends the lifespan of fruit flies works by limiting free radicals
and the damage they cause. Free radicals are highly reactive cellular
byproducts that damage tissue and contribute to many of the signs of
aging.

Professor Stephen Helfand of Brown's Department of Molecular Biology,
Cell Biology and Biochemistry and his associates sought to determine
the life-extending mechanism of a mutation named "Indy" (which stands
for "I'm not dead yet"), that he first discovered in 2000. Flies with
the Indy mutation have double the average life span as those without
it (70 versus 35 days). Dr Helfand's team compared gene expression in
Indy flies and normal flies throughout their lives and determined
that the mutation significantly limits the production of free
radicals known as reactive oxygen species via reduced expression of
genes involved in generating energy, without decreasing the overall
level of energy (as assessed by measuring adenosine triphosphate
levels) within the cell. Accordingly, protein carbonyls, a measure of
free radical damage to proteins, were lower in the mitochondrial
protein of Indy flies.

"There are very few, if any, interventions that are known to
dramatically extend healthy lifespan," Dr Helfand
stated. "Understanding how … the Indy mutation alters the metabolic
state of the fruit fly would allow someone to come up with
pharmacological interventions that could mimic it and give you the
benefit of genetic manipulation without having to do genetics."