Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian .

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 3 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 to be irreversibly reduced in aging but 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.