TY - JOUR
T1 - TGF-β and Insulin Signaling Regulate Reproductive Aging via Oocyte and Germline Quality Maintenance
AU - Luo, Shijing
AU - Kleemann, Gunnar A.
AU - Ashraf, Jasmine M.
AU - Shaw, Wendy M.
AU - Murphy, Coleen T.
N1 - Funding Information:
We thank Cathy Savage-Dunn (CUNY) for CS122 and pCS227; David Sherwood (Duke University) for NK640; Barth Grant (Rutgers) for RT130 and α-RME-2 antibody; members of the Murphy Laboratory and Z. Gitai for comments on the manuscript; and March of Dimes Basil O'Connor Starting Scholar, NIH New Innovator (1DP2OD004402-01), and NIH (P50 GM071508) awards for funding.
PY - 2010/10/15
Y1 - 2010/10/15
N2 - 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:
AB - 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:
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U2 - 10.1016/j.cell.2010.09.013
DO - 10.1016/j.cell.2010.09.013
M3 - Article
C2 - 20946987
AN - SCOPUS:77957797819
SN - 0092-8674
VL - 143
SP - 299
EP - 312
JO - Cell
JF - Cell
IS - 2
ER -