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Deficient autophagy drives aging in Hydra

Fischer, Kathleen
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Submitted to BioRxiv. 2017
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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 coldsensitive (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.
Keywords Hydra model systemAging mechanismsRegenerationEpithelial stem cellsAutophagyProteostasisRapamycinP62/SQSTM1ULK1WIPI2
Note supplemental file: Methods, 10 supplemental Figures, one Table and four Movies
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Projects FNS: 31003A_149630; 31003_169930
NH grant R01AG037962
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TOMCZYK, Szymon et al. Deficient autophagy drives aging in Hydra. Submitted to: BioRxiv , 2017. https://archive-ouverte.unige.ch/unige:101701

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Deposited on : 2018-01-29

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