TGF-β and Insulin Signaling Regulate Reproductive Aging via Oocyte and Germline Quality Maintenance

Shijing Luo, Gunnar A. Kleemann, Jasmine M. Ashraf, Wendy M. Shaw, Coleen T. Murphy

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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. PaperClip:

Original languageEnglish (US)
Pages (from-to)299-312
Number of pages14
JournalCell
Volume143
Issue number2
DOIs
StatePublished - Oct 15 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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