Abstract：
:Egg production declines with age in many species, a process linked with stem cell loss. Diet-dependent signaling has emerged as critical for stem cell maintenance during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF signaling (IIS), entering quiescence in the absence of nutrients and initiating proliferation rapidly upon feeding. Although highly proliferative FSCs generally exhibit an extended lifespan, we find that constitutive Hh signaling drives FSC loss and premature sterility despite high proliferative rates. This occurs due to Hh-mediated induction of autophagy in FSCs via a Ptc-dependent, Smo-independent mechanism. Hh-dependent autophagy increases during aging, triggering FSC loss and consequent reproductive arrest. IIS is necessary and sufficient to suppress Hh-induced autophagy, promoting a stable proliferative state. These results suggest that opposing action of diet-responsive IIS and Hh signals determine reproductive lifespan by modulating the proliferation-autophagy balance in FSCs during aging.
journal_name
Dev Celljournal_title
Developmental cellauthors
Singh T,Lee EH,Hartman TR,Ruiz-Whalen DM,O'Reilly AMdoi
10.1016/j.devcel.2018.08.008subject
Has Abstractpub_date
2018-09-24 00:00:00pages
720-734.e6issue
6eissn
1534-5807issn
1878-1551pii
S1534-5807(18)30678-6journal_volume
46pub_type
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