Deficient autophagy drives aging in Hydra

TOMCZYK, S.; SCHENKELAARS, Q.; SUKNOVIC, N.; WENGER, Y.; EKUNDAYO, K.; BUZGARIU, W.; BAUER, C.; FISCHER, K. E.; AUSTAD, S.; GALLIOT, B.

doi:10.1101/236638

bioRxiv · 10.1101/236638

Deficient autophagy drives aging in Hydra

TOMCZYK, S.·SCHENKELAARS, Q.·SUKNOVIC, N.·WENGER, Y.·EKUNDAYO, K.·BUZGARIU, W.·BAUER, C.·FISCHER, K. E.·AUSTAD, S.·GALLIOT, B.

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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 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.

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TOMCZYK, S., SCHENKELAARS, Q., SUKNOVIC, N., WENGER, Y., EKUNDAYO, K., BUZGARIU, W., BAUER, C., FISCHER, K. E., AUSTAD, S., GALLIOT, B.. 2017-12-23. Deficient autophagy drives aging in Hydra. https://doi.org/10.1101/236638

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