Notch signaling in germ line stem cells controls reproductive aging in Caenorhabditis elegans.

Abstract

Adult stem cells maintain and rejuvenate a wide range of tissues, and the progressive, age-related decline of adult stem cells is a hallmark of aging. We propose that the Caenorhabditis elegans germline is an experimentally tractable model of adult stem cell aging and that stem cell exhaustion is a cause of reproductive senescence. Because these are the only stem cells in adult worms, this system provides a unique opportunity to exploit the power of C. elegans to address stem cell exhaustion during aging. Here, we show that reproductive aging occurs early in adult life in multiple species in the genus Caenorhabditis, indicating that this is a feature of both female/male and hermaphrodite/male species. Our results indicate that cellular and molecular changes in germline stem cells are a cause of reproductive aging, since we demonstrated that defects in stem cell number and activity were well correlated with extended progeny production in daf-2, eat-2, and phm-2 C. elegans mutants. Ectopic expression of the Notch effector SYGL-1 in germ line stem cells was sufficient to delay stem cell aging, indicating that the conserved Notch pathway can act cell autonomously to control age-related decline of adult stem cells. These animals displayed increased progeny production in midlife without a depression of early progeny production, a pattern of reproductive aging distinct from previous mutants. These results suggest that age-related declines of stem cell number and activity are a cause of reproductive aging in C. elegans and the Notch signaling pathway may be a control point that mediates this decline.