A metabolic adaptation in muscle mediates the protective effects of dietary restriction in Drosophila. Subhash D. Katewa, Kazutaka Akagi, Matthew J. Laye, Pankaj Kapahi. Buck Institute for Research on Aging, Novato, CA.

   Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. We recently showed that upon DR, Drosophila melanogaster shift their metabolism towards increasing fat turnover, which is required for various responses to DR. Inhibition of fatty acid synthesis or oxidation genes specifically in the muscle tissue reduced spontaneous activity and inhibited lifespan extension upon DR. Reducing spontaneous activity of the flies by physical or genetic manipulations also reduced the DR dependent lifespan extension. Now, we report that d4E-BP (Drosophila eIF-4E binding protein), a downstream target of the TOR pathway mediates the DR dependent increases in fat turnover and spontaneous activity. Muscle specific over-expression of d4E-BP increased spontaneous activity, enhanced fat metabolism in fat bodies and was sufficient to increase lifespan in a nutrient dependent manner. The regulation of fat metabolism in a distant tissue such as fat bodies by muscle indicates involvement of myokines- muscle specific secreted factors. Together these results suggest a critical role of muscle specific d4E-BP in regulating whole body physiology, metabolism and aging upon DR.