TGF-β and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance.

TitleTGF-β and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance.
Publication TypeJournal Article
Year of Publication2010
AuthorsLuo S, Kleemann GA, Ashraf JM, Shaw WM, Murphy CT
JournalCell
Volume143
Issue2
Pagination299-312
Date Published2010 Oct 15
ISSN1097-4172
KeywordsAging, Animals, Apoptosis, Caenorhabditis elegans, Humans, Insulin, Oocytes, Reproduction, Signal Transduction, Transforming Growth Factor beta
Abstract

Reproductive cessation is perhaps the earliest aging phenotype that humans experience. Similarly, reproduction of Caenorhabditis elegans ceases in mid-adulthood. Although somatic aging has been studied in both worms and humans, mechanisms regulating reproductive aging are not yet understood. Here, we show that TGF-β Sma/Mab and Insulin/IGF-1 signaling regulate C. elegans reproductive aging by modulating multiple aspects of the reproductive process, including embryo integrity, oocyte fertilizability, chromosome segregation fidelity, DNA damage resistance, and oocyte and germline morphology. TGF-β activity regulates reproductive span and germline/oocyte quality noncell-autonomously and is temporally and transcriptionally separable from its regulation of growth. Chromosome segregation, cell cycle, and DNA damage response genes are upregulated in TGF-β mutant oocytes, decline in aged mammalian oocytes, and are critical for oocyte quality maintenance. Our data suggest that C. elegans and humans share many aspects of reproductive aging, including the correlation between reproductive aging and declining oocyte quality and mechanisms determining oocyte quality.

DOI10.1016/j.cell.2010.09.013
Alternate JournalCell
Full Text
PubMed ID20946987
PubMed Central IDPMC2955983
Grant ListDP2 OD004402 / OD / NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
1DP2OD004402-01 / OD / NIH HHS / United States