Dietary restriction (DR) extends lifespan in many organisms ranging from simple invertebrates to complex mammals. A number of lifespan extending DR regimens have been described in diverse organisms, but it is still not clear if there are universal or overlapping mechanisms that modulate longevity by DR. In C. elegans, there are many ways to induce DR and different methods elicit varied downstream responses, revealing a complex process. Although a handful of important regulators have been identified, the molecular basis of DR mediated longevity still remains poorly understood, and additional players are likely to be involved.
From a genetic screen for DR longevity mediators, we identified the RING finger protein NCL-1 to be required for DR induced longevity. ncl-1 is known to regulate the nucleolar size in worms and the loss of ncl-1 leads to increased nucleolar size and also increased translation. Our data suggest that nucleolar size is reduced under DR conditions and that the loss of ncl-1 abrogates DR longevity as well as the longevity conferred by the inhibition of the TOR pathway. The TOR pathway is known to be involved in DR mediated longevity and it also regulates translation. Global translation levels are low under DR conditions. So we speculate ncl-1 loss might be altering the translational rates thus abrogating longevity under DR and TOR inhibition. We are now investigating how ncl-1 interacts with nutrient sensing pathways and its detailed role in influencing lifespan extension. These studies should provide greater molecular insights into DR mediated longevity and a link between TOR signaling, translation and longevity under DR conditions. .
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