Mechanisms underlying longevity by dietary restriction in C. elegans: role of the energy sensor AMPK
Dietary restriction (DR) is the most effective intervention to extend lifespan in virtually all species. DR also decreases the onset of wide range of age-dependent diseases. However, the mechanisms that underlie the benefits of DR on lifespan and healthspan are just starting to be understood.
Our lab has played an important role in identifying new genes and pathways that mediate longevity induced by DR. We used the nematode C. elegans to interrogate the mechanisms of DR-induced longevity. Our studies identified the energy-sensing protein kinase AMPK as a pivotal gene that mediates longevity induced by some DR regimens in C. elegans. We showed that AMPK extends lifespan in worms in part by acting on DAF-16, the worm FOXO transcription factor (Greer et al, Current Biology, 2007). Our findings also revealed that DR extends lifespan by triggering independent, yet overlapping, signaling pathways (Greer et al, Aging Cell, 2009). Our studies were the first to show the importance of AMPK and FOXO in longevity in response to some DR regimens. We also made the significant contribution to the field that DR elicits a network of non-overlapping pathways, rather than a common pathway, which is a pivotal for harnessing the entire benefits of DR on healthspan and lifespan.
Greer EL, Dowlatshahi D, Banko MR, Hoang K, Blanchard D and Brunet A (2007) An AMPK-FOXO pathway mediates the extension of lifespan induced by a novel method of dietary restriction in C. elegans. Current Biology, 17: 1646-1656. Abstract PDF