possesses three distinct stem cell populations that continuously self-renew and prevent aging in However sexual animals from the cold-sensitive ( strain develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within three months. This phenotype is not observed in the cold-resistant strain. To dissect the mechanisms of aging we compared the self-renewal of epithelial stem cells in these two strains and found it irreversibly reduced in aging while sustained in non-aging We also identified a deficient autophagy in epithelial cells, with a constitutive deficiency in autophagosome formation as detected with the mCherry-eGFP-LC3A/B autophagy sensor, an inefficient response to starvation as evidenced by the accumulation of the autophagosome cargo protein p62/SQSTM1, and a poorly-inducible autophagy flux upon proteasome inhibition. In the non-aging animals, the blockade of autophagy by knocking-down suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.
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