Enhanced Energy Metabolism Contributes to Extended Lifespan Through Calorie Restriction

Here is an open access paper that looks at some of the mechanisms of calorie restriction in nematode worms - and you'll note that PEPCK-C manipulation, shown to extend life and improve health in mice, also works in the same way in this lower species: "Caloric restriction (CR) markedly extends lifespan and improves the health of a broad number of species. Energy metabolism fundamentally contributes to the beneficial effects of CR, but the underlying mechanisms that are responsible for this effect remain enigmatic. A multidisciplinary approach that involves quantitative proteomics, immunochemistry, metabolic quantification and lifespan analysis was used to determine how CR, which occurs in the C. elegans eat-2 mutants, modifies energy metabolism of the worm, and whether the observed modifications contribute to the CR-mediated physiological responses. A switch to fatty acid metabolism as an energy source and an enhanced rate of energy metabolism by eat-2 mutant nematodes was detected. Lifespan analyses validated the important role of these previously unknown alterations of energy metabolism in the CR-mediated longevity of nematodes. As observed in mice, the over-expression of the gene for the nematode analogue of the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C) caused a marked extension of lifespan in C. elegans, presumably by enhancing energy metabolism ... We conclude that an increase, not a decrease in fuel consumption, via an accelerated oxidation of fuels in the TCA cycle is involved in lifespan regulation; this mechanism may be conserved across phylogeny."

Link: http://dx.doi.org/10.1074/jbc.M112.377275

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