Deficient autophagy drives aging in Hydra

S Tomczyk, Q Schenkelaars, N Suknovic, Y Wenger… - BioRxiv, 2017 - biorxiv.org
S Tomczyk, Q Schenkelaars, N Suknovic, Y Wenger, K Ekundayo, W Buzgariu, C Bauer…
BioRxiv, 2017biorxiv.org
Hydra exhibits a negligible senescence as its epithelial and interstitial stem cell populations
continuously divide. Here we identified two H. oligactis strains that respond differently to
interstitial stem cell loss. Cold-resistant (Ho_CR) animals adapt and remain healthy while
cold-sensitive (Ho_CS) ones die within three months, after their epithelial stem cells lose
their selfrenewal potential. In Ho_CS but not in Ho_CR animals, the autophagy flux is
deficient, characterized by a low induction upon starvation, proteasome inhibition or …
Abstract
Hydra exhibits a negligible senescence as its epithelial and interstitial stem cell populations continuously divide. Here we identified two H. oligactis strains that respond differently to interstitial stem cell loss. Cold-resistant (Ho_CR) animals adapt and remain healthy while cold-sensitive (Ho_CS) ones die within three months, after their epithelial stem cells lose their selfrenewal potential. In Ho_CS but not in Ho_CR animals, the autophagy flux is deficient, characterized by a low induction upon starvation, proteasome inhibition or Rapamycin treatment, and a constitutively repressed Ulk activity. In the non-aging Hydra vulgaris, WIPI2 silencing suffices to induce aging. Rapamycin can delay aging by sustaining epithelial self-renewal and regeneration, although without enhancing the autophagy flux. Instead Rapamycin promotes engulfment in epithelial cells where p62/SQSTM1-positive phagocytic vacuoles accumulate. This study uncovers the importance of autophagy in the longevity of early-branched eumetazoans by maintaining stem cell renewal, and a novel anti-aging effect of Rapamycin via phagocytosis.
biorxiv.org
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