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

Development. 2020 Jan 23;147(2):dev177840. doi: 10.1242/dev.177840.


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; Evolution of aging; Hydra regeneration; Rapamycin; WIPI2; p62/SQSTM1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Autophagy* / drug effects
  • Cell Proliferation / drug effects
  • Cold Temperature
  • Epidermis / drug effects
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Fresh Water*
  • Gametogenesis / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Hydra / drug effects
  • Hydra / genetics
  • Hydra / physiology*
  • Imaging, Three-Dimensional
  • Phenotype
  • Proteasome Inhibitors / pharmacology
  • Sirolimus / pharmacology
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Survival Analysis


  • Proteasome Inhibitors
  • Sirolimus