Abstract
A major challenge in translating the positive
effects of dietary restriction (DR) for the improvement of human health is
the development of therapeutic mimics. One approach to finding DR mimics
is based upon identification of the proximal effectors of DR life span
extension. Whole genome profiling of DR in
Drosophila
shows a large
number of changes in gene expression, making it difficult to establish
which changes are involved in life span determination as opposed to other
unrelated physiological changes. We used comparative whole genome expression
profiling to discover genes whose change in expression is shared between DR
and two molecular genetic life span extending interventions related to DR,
increased dSir2 and decreased Dmp53 activity. We find twenty-one genes
shared among the three related life span extending interventions. One of
these genes,
takeout,
thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions:
Rpd3,
Indy
,
chico
and
methuselah
. We demonstrate
takeout
is involved in longevity determination by specifically increasing adult
takeout
expression and extending life span. These studies demonstrate the power of
comparative whole genome transcriptional profiling for identifying specific
downstream elements of the DR life span extending pathway.