Germline proliferation and differentiation during aging

Stem cells maintain tissues and organs over the lifespan of individuals, but how aging influences this process is unclear. We investigated the effects of aging on the C. elegans germline stem/progenitor cells. We found that the progenitor pool is depleted over time in a manner dependent on inhibition of DAF-16/FOXO by insulin/IGF-1 signalling (IIS). Further, we found 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.

Relevant Publications:

Non-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans germline stem/progenitor cells. Qin Z, Hubbard EJ. Nat Commun. 2015 May 11;6:7107. doi: 10.1038/ncomms8107.

Projects:

Regulation of germline proliferation and differentiation by the environment: insulin, TOR and TGFß

Germline proliferation and differentiation during aging

Stem cell dynamics: in vivo and in silico

Regulation of germline proliferation and differentiation by direct cell-cell communication: sheath cell-germline signaling