Loss of foxo rescues stem cell aging in Drosophila germ line

Author:

Artoni Filippo12ORCID,Kreipke Rebecca E12ORCID,Palmeira Ondina123,Dixon Connor12,Goldberg Zachary12,Ruohola-Baker Hannele12ORCID

Affiliation:

1. Department of Biochemistry, University of Washington, Seattle, United States

2. Institute for Stem Cell and Regenerative Medicine, University of Washington, School of Medicine, Seattle, United States

3. Nucleus of Multidisciplinary Research, Universidade Federal do Rio de Janeiro, Duque de Caxias, Brazil

Abstract

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.

Funder

National Institute on Aging

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

National Institute of General Medical Sciences

Hahn Family

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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