Qin Zhao, Hubbard E Jane Albert
Departments of Cell Biology and Pathology, The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, New York, USA.
Nat Commun. 2015 May 11;6:7107. doi: 10.1038/ncomms8107.
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.
干细胞在个体的整个生命周期中维持组织和器官的功能。衰老如何影响这一过程尚不清楚。在这里，我们研究了衰老对秀丽隐杆线虫生殖系干细胞/祖细胞的影响，并表明祖细胞池会随着时间的推移而减少，其方式依赖于胰岛素/胰岛素样生长因子-1信号通路（IIS）对DAF-16/FOXO的抑制作用。我们的数据表明，某些体细胞性腺细胞中的DAF-16/FOXO活性是生殖系祖细胞维持所必需的，并且这一作用与DAF-16/FOXO对机体衰老的影响是可分离的。此外，阻断生殖细胞通量，类似于降低IIS，可维持生殖系祖细胞。这种效应部分依赖于性腺中的DAF-16/FOXO活性。我们的结果表明：（1）长寿通路可通过解剖学上可分离的机制调节衰老的干细胞；（2）干细胞的维持不一定具有优先性；（3）干细胞调节可发生在整个器官系统水平，如生殖系统。
