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.
Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The Genetics Society of America
9650 Rockville Pike, Bethesda, MD
Phone: 301-634-7300, Fax: 301-634-7079
Questions and Comments: firstname.lastname@example.org