Deficient autophagy drives aging in Hydra

Tomczyk, Szymon; Schenkelaars, Quentin; Suknovic, Nenad; Wenger, Yvan; Ekundayo, Kazadi; Buzgariu, Wanda Christa; Bauer, Christoph Ruediger; Fischer, Kathleen; Austad, Steven; Galliot, Brigitte

doi:10.1101/236638

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Title		Deficient autophagy drives aging in Hydra
Authors		Tomczyk, Szymon Schenkelaars, Quentin Suknovic, Nenad Wenger, Yvan Ekundayo, Kazadi Buzgariu, Wanda Christa Bauer, Christoph Ruediger Fischer, Kathleen Austad, Steven Galliot, Brigitte show all authors [1 - 10]
Submitted to		BioRxiv. 2017
Description		16
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 system — Aging mechanisms — Regeneration — Epithelial stem cells — Autophagy — Proteostasis — Rapamycin — P62/SQSTM1 — ULK1 — WIPI2
Identifiers		DOI: 10.1101/236638
Note		supplemental file: Methods, 10 supplemental Figures, one Table and four Movies
Full text		Article (Preprint) (4 MB) - Free access Other version: http://www.biorxiv.org/content/early/2017/12/23/236638
Structures		Faculté des sciences / Section de biologie / Département de génétique et évolution
Projects		FNS: 31003A_149630; 31003_169930 NH grant R01AG037962
Citation (ISO format)		TOMCZYK, Szymon et al. Deficient autophagy drives aging in Hydra. Submitted to: BioRxiv , 2017. doi: 10.1101/236638 https://archive-ouverte.unige.ch/unige:101701