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Development. 2020 Jan 23;147(2). pii: dev177840. doi: 10.1242/dev.177840.

Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra.

Author information

1
Department of Genetics and Evolution, Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1205 Geneva, Switzerland.
2
Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
3
Department of Genetics and Evolution, Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1205 Geneva, Switzerland brigitte.galliot@unige.ch.

Abstract

Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris However, sexual animals from the H. oligactis cold-sensitive strain Ho_CS develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within 3 months. This phenotype is not observed in the cold-resistant strain Ho_CR To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it to be irreversibly reduced in aging Ho_CS but sustained in non-aging Ho_CR We also identified a deficient autophagy in Ho_CS epithelial cells, with a constitutive deficiency in autophagosome formation as detected with the mCherry-eGFP-LC3A/B autophagy sensor, an inefficient response to starvation as evidenced by the accumulation of the autophagosome cargo protein p62/SQSTM1, and a poorly inducible autophagy flux upon proteasome inhibition. In the non-aging H. vulgaris animals, the blockade of autophagy by knocking down WIPI2 suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.

KEYWORDS:

Aging model system; Autophagy sensor; Epithelial stem cells; Evolution of aging; Hydra regeneration; Rapamycin; WIPI2; p62/SQSTM1

PMID:
31862842
DOI:
10.1242/dev.177840
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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