insulin signaling pathway—a well-known regulator of aging

Energy Sensors: Insulin–PI3K, SIR2,AMPK, TOR

Insulin levels are potently regulated by nutrients,raising the possibility that the insulin signaling
pathway—a well-known regulator of aging may play a role in mediating DR.
While insulin levels are indeed decreased by DR in mammals , it is not clear whether
insulin-like peptides or the activity of the insulin signaling pathway is decreased by DR in C. elegans.
FoxO/daf-16 nuclear translocation, which is a consequence of the inactivation of the insulin signaling
pathway, does not appear to be affected by many DR methods , although starvation
and IF both trigger FoxO/daf-16 nuclear translocation mutants of the insulin receptor daf-2 or of age-1,which encodes the C. elegans ortholog of the catalytic subunit of PI3K, still display an extension of life span in response to BDR that is equivalent to that of the
wild type (WT). Such a result suggests that daf-2 and age-1 are not necessary for BDR to extend life span.

Similarly, daf-2 mutants still display extension of life span to the same extent as WT in response to
sDR , eat-2 , and BD/DD . Axenic medium and a modified form
of BDR, termed LDR in this review, also extend the life span of daf-2 worms significantly more than thatof WT worms . Consistent with a limited involvement of the insulin signaling pathway in life-span extension by DR, the life span of FoxO/daf-16 null mutant worms is still increased by many methods of DR

Mammals: SIR2, TOR,Insulin–FoxO, NFE2

Several dietary manipulations extend life span in rodents. The most frequently used is called CR
(caloric restriction) and corresponds to a 40% reduction in the total amount of food.