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Scientific article
Open access
English

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

Published inDevelopment, vol. 147, no. dev177840, p. 1-16
Publication date2020
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 system
  • Autophagy sensor
  • Epithelial stem cells
  • Hydra regeneration
  • Evolution of aging
  • p62/SQSTM1
  • WIPI2
  • Rapamycin
Research group
Funding
  • Swiss National Science Foundation - 31003A_149630, 31003_169930
  • Autre - NIH R01AG037962
Citation (ISO format)
TOMCZYK, Szymon et al. Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian <i>Hydra</i>. In: Development, 2020, vol. 147, n° dev177840, p. 1–16. doi: 10.1242/dev.177840

Technical informations

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