TY - JOUR T1 - Deficient autophagy drives aging in <em>Hydra</em> JF - bioRxiv DO - 10.1101/236638 SP - 236638 AU - Szymon Tomczyk AU - Quentin Schenkelaars AU - Nenad Suknovic AU - Yvan Wenger AU - Kazadi Ekundayo AU - Wanda Buzgariu AU - Christoph Bauer AU - Kathleen Fischer AU - Steven Austad AU - Brigitte Galliot Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/12/23/236638.abstract N2 - 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. ER -