Stem cells maintain tissues and organs over the lifespan of individuals. How aging influences this process is unclear. Here we use the C. elegans germ line as a model to study stem cell aging. The C. elegans germ line combines a well-established genetic model for aging studies with a well-defined, accessible stem cell system, providing a unique opportunity to dissect the effects of aging on stem cell dynamics.
We found that the stem/progenitor cell pool in the C. elegans germ line becomes depleted over time. This depletion is suppressed in mutants with reduced insulin/IGF-like signaling (IIS) via the downstream transcription factor DAF-16/FOXO. DAF-16/FOXO acts neither in the germ line itself nor in the intestine, suggesting that DAF-16/FOXO regulates age-related germline stem/progenitor cell loss through a novel mechanism that is anatomically separable from its previously described roles in larval germline proliferation and lifespan regulation. Further, we found that DAF-16/FOXO activity is required in the proximal region of the somatic gonad, suggesting that the part of the reproductive system that experiences the transit of gametes and/or embryos might signal to and influence the stem/progenitor cell pool. Consistent with this hypothesis, we found that animals with an altered rate of germ cell flux through the reproductive tract lose their germline stem/progenitor cells at a significantly different rate compared with controls and that DAF-16/FOXO partially mediates the effect of germ cell flux on germline stem/progenitor cell maintenance over time. Together, our results represent a novel mechanism of stem cell regulation at the organ level in addition to regulation of stem cells by their niche and the systemic environment of the organism.
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