Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra
| Autor: | Steven N. Austad, Nenad Slavko Suknovic, Kazadi Ekundayo, Quentin Schenkelaars, Brigitte Galliot, Yvan Wenger, Christoph Ruediger Bauer, Wanda Christa Buzgariu, Szymon Tomczyk, Kathleen E. Fischer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Autophagosome
Aging WIPI2 Hydra p62/SQSTM1 Hydra regeneration Fresh Water Gametogenesis 03 medical and health sciences 0302 clinical medicine Imaging Three-Dimensional ddc:590 Autophagy Animals Rapamycin Molecular Biology Autophagy sensor 030304 developmental biology Cell Proliferation Sirolimus 0303 health sciences biology Stem Cells Aging model system Gene Expression Regulation Developmental Evolution of aging Epithelial Cells biology.organism_classification Stem Cells and Regeneration Phenotype Survival Analysis Cell biology Cold Temperature Hydra vulgaris Lernaean Hydra Stem cell Epidermis Epithelial stem cells Flux (metabolism) Proteasome Inhibitors 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Development (Cambridge, England) Development, Vol. 147, No dev177840 (2020) pp. 1-16 |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | 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. Summary: Lack of epithelial stem cell renewal and deficient epithelial autophagy are the major causes of aging in Hydra oligactis, whereas lowering autophagy efficiency in the non-aging Hydra vulgaris induces an aging phenotype. |
| Databáze: | OpenAIRE |
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