Abstract
Stem cells maintain tissues and organs over the lifespan of individuals. How aging influences this process is unclear. Here we investigate the effects of aging on C. elegans germline stem/progenitor cells and show that the progenitor pool is depleted over time in a manner dependent on inhibition of DAF-16/FOXO by insulin/IGF-1 signalling (IIS). Our data indicate that DAF-16/FOXO activity in certain somatic gonad cells is required for germline progenitor maintenance, and that this role is separable from the effect of DAF-16/FOXO on organismal aging. In addition, blocking germ cell flux, similar to reducing IIS, maintains germline progenitors. This effect is partially dependent on gonadal DAF-16/FOXO activity. Our results imply that (1) longevity pathways can regulate aging stem cells through anatomically separable mechanisms, (2) stem cell maintenance is not necessarily prioritized and (3) stem cell regulation can occur at the level of an entire organ system such as the reproductive system.
Highlights
Stem cells maintain tissues and organs over the lifespan of individuals
By modulating DAF16/FOXO activity in a tissue-specific manner, we found that the extent of germline progenitor loss over time could be uncoupled from the rate of organismal aging
Our results show that (1) the stem/progenitor cell pool in the C. elegans germ line becomes depleted over time; (2) reducing insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) maintains this pool through DAF-16/FOXO activity in the proximal somatic gonad; and (3) blocking germ cell flux maintains germline progenitors and this effect partially depends on proximal somatic gonad DAF-16/FOXO activity (Fig. 4d)
Summary
Stem cells maintain tissues and organs over the lifespan of individuals How aging influences this process is unclear. We investigate the effects of aging on C. elegans germline stem/progenitor cells and show that the progenitor pool is depleted over time in a manner dependent on inhibition of DAF-16/FOXO by insulin/IGF-1 signalling (IIS). Blocking germ cell flux, similar to reducing IIS, maintains germline progenitors This effect is partially dependent on gonadal DAF-16/FOXO activity. We investigated the effects of age on the pool of undifferentiated proliferative cells in the distal end of the C. elegans germ line This population of cells includes both germline stem cells and their proliferative progeny (hereafter referred to as ‘germline progenitor cells’, as no markers currently distinguish stem cells from their proliferative progeny; Fig. 1a). We determined that germ cell flux influences germline progenitor maintenance through DAF-16/FOXO-dependent and DAF-16/FOXO-independent mechanisms
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