Loss of foxo rescues stem cell aging in Drosophila germ line
نویسندگان
چکیده
Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.
منابع مشابه
Non-autonomous DAF-16/FOXO activity antagonizes age-related loss of C. elegans germline stem/progenitor cells
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 cer...
متن کاملDrosophila germ-line modulation of insulin signaling and lifespan.
Ablation of germ-line precursor cells in Caenorhabditis elegans extends lifespan by activating DAF-16, a forkhead transcription factor (FOXO) repressed by insulin/insulin-like growth factor (IGF) signaling (IIS). Signals from the gonad might thus regulate whole-organism aging by modulating IIS. To date, the details of this systemic regulation of aging by the reproductive system are not understo...
متن کاملA Transcription Elongation Factor That Links Signals from the Reproductive System to Lifespan Extension in Caenorhabditis elegans
In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this proces...
متن کاملI-18: Avian Chimeras and Germ Cell Migration
Background: In avian species, the germ line stem cell population arises outside of the embryonic gonad and proceeds on a circuitous migration to the germinal epithelium. Specifically, in the avian embryo, the process of germ line stem cell migration proceeds through a series of active and passive migratory phases. The germline stem cells or primordial germ cells (PGCs) located in the epiblast o...
متن کاملDrosophila CG2469 Encodes a Homolog of Human CTR9 and Is Essential for Development
Conserved from yeast to humans, the Paf1 complex participates in a number of diverse processes including transcriptional initiation and polyadenylation. This complex typically includes five proteins: Paf1, Rtf1, Cdc73, Leo1, and Ctr9. Previous efforts identified clear Drosophila homologs of Paf1, Rtf1, and Cdc73 based on sequence similarity. Further work showed that these proteins help to regul...
متن کامل