@article{624bc8c456a648e8a0ca54895639d28c,
title = "Rapid population-wide declines in stem cell number and activity during reproductive aging in C. elegans",
abstract = "C. elegans hermaphrodites display dramatic age-related decline of reproduction early in life, while somatic functions are still robust. To understand reproductive aging, we analyzed the assembly line of oocyte production that generates fertilized eggs. Aging germlines displayed both sporadic and population-wide changes. A small fraction of aging animals displayed endomitotic oocytes in the germline and other defects. By contrast, all animals displayed age-related decreases in germline size and function. As early as day 3 of adulthood, animals displayed fewer stem cells and a slower cell cycle, which combine to substantially decrease progenitor zone output. The C. elegans germline is the only adult tissue that contains stem cells, allowing the analysis of stem cells in aging. To investigate the mechanism of the decrease in stem cell number, we analyzed the Notch signaling pathway. The Notch effectors LST-1 and SYGL-1 displayed agerelated decreases in expression domains, suggesting a role for Notch signaling in germline aging. The results indicate that although sporadic defects account for the sterility of some animals, population-wide changes account for the overall pattern of reproductive aging.",
keywords = "Caenorhabditis, Cell cycle, Endomitotic oocytes, Germline, Meiotic development, Notch, Reproductive aging, Stem cells",
author = "Zuzana Kocsisova and Kerry Kornfeld and Tim Schedl",
note = "Funding Information: This work was supported in part by the National Institutes of Health (R01 AG02656106A1 to K.K., R01 GM100756 to T.S.), by a National Science Foundation predoctoral fellowship (DGE-1143954 and DGE-1745038 to Z.K.) and by The Douglas Covey Fellowship to Z.K. The National Institutes of Health, the National Science Foundation and Douglas Covey had no role in the design of the study, collection, analysis and interpretation of data, or in writing the manuscript. Deposited in PMC for release after 12 months. Funding Information: We are grateful to the E. coli stock center for MG1693; to Wormbase; to the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health Office of Research Infrastructure Programs (P40OD010440), for strains; to Mike Nonet and Scott Dour for advice, reagents and injection microscope use for CRISPR/Cas9 genome engineering; to Zach Pincus for statistical advice and injection microscope use; to Aiping Feng for reagents; to Luke Schneider, Andrea Scharf, Sandeep Kumar, Ariz Mohammad and John Brenner for training, advice, support, reagents and helpful discussion; and to the Kornfeld and Schedl labs for feedback on this manuscript. Finally, we are grateful to three anonymous reviewers for suggestions that greatly improved the manuscript. Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd.",
year = "2019",
month = apr,
day = "15",
doi = "10.1242/dev.173195",
language = "English",
volume = "146",
journal = "Development",
issn = "0950-1991",
number = "8",
}