Intestinal Autophagy Important in Calorie Restriction and Longevity in Nematodes

Based on the evidence accumulated from many years of studies of flies and nematodes, intestinal function is fairly central in aging and longevity. This is one of those things that probably doesn't translate so well to higher, more complex, and larger species, but the general principle of better organ function correlating to better health and a longer life expectancy is something to hold on to. In this open access paper the the increased activity of the cellular housekeeping mechanisms of autophagy, produced alongside greater longevity by the practice of calorie restriction, is investigated in the context of intestinal function in nematodes:

Dietary restriction (DR) without inducing malnutrition has robust beneficial effects on lifespan in many species, including humans. The cellular recycling process of autophagy contributes to DR-mediated longevity. Autophagy is triggered by nutrient scarcity and increases the degradation of cytosolic molecules and organelles in the lysosomes. Using the nematode Caenorhabditis elegans as a model organism, we previously showed that genes involved in autophagy are required for lifespan extension through DR; however, it is not clear whether autophagy in individual tissues plays critical roles in DR-mediated longevity.

Here, we investigated the contribution of autophagy in genetically dietary-restricted eat-2 mutants. Our major findings include: (i) Inhibition of autophagy in the intestine prevents the long lifespan observed in eat-2 mutants; (ii) the intestine of eat-2 mutants contains an expanded lysosomal compartment and flux assays indicate increased autophagosome turnover, consistent with elevated autophagy in this tissue; (iii) intestinal autophagy is required for the improved intestinal integrity observed in eat-2 mutants; (iv) autophagy inhibition impairs motility in older animals; and (v) inhibition of autophagy in the intestine accelerates the motility decline in eat-2 mutants. Collectively, these studies suggest a critical role for intestinal autophagy in dietary-restricted animals, and highlight the importance of this process in maintaining fitness and longevity.



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