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

Fischer, Kathleen
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Published in Development. 2020, vol. 147, no. dev177840, p. 1-16
Abstract Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris. However, sexual animals from the H. oligactis cold-sensitive strain Ho_CS 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 Ho_CR. To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it to be irreversibly reduced in aging Ho_CS but sustained in non-aging Ho_CR. We also identified a deficient autophagy in Ho_CS 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 H. vulgaris animals, the blockade of autophagy by knocking down WIPI2 suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.
Keywords Aging model systemAutophagy sensorEpithelial stem cellsHydra regenerationEvolution of agingp62/SQSTM1WIPI2Rapamycin
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Research group Groupe Galliot
Swiss National Science Foundation: 31003A_149630, 31003_169930
Autre: NIH R01AG037962
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TOMCZYK, Szymon et al. Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra. In: Development, 2020, vol. 147, n° dev177840, p. 1-16. doi: 10.1242/dev.177840 https://archive-ouverte.unige.ch/unige:129365

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Deposited on : 2020-01-24

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