Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.

Aging in Caenorhabditis elegans is characterized by widespread physiological and molecular changes, but the mechanisms that determine the rate at which these changes occur are not well understood. In this study, we identify a novel link between reproductive aging and somatic aging in C. elegans. By...

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Main Authors: Stephanie M Zimmerman, Izumi V Hinkson, Joshua E Elias, Stuart K Kim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-12-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005725&type=printable
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author Stephanie M Zimmerman
Izumi V Hinkson
Joshua E Elias
Stuart K Kim
author_facet Stephanie M Zimmerman
Izumi V Hinkson
Joshua E Elias
Stuart K Kim
author_sort Stephanie M Zimmerman
collection DOAJ
description Aging in Caenorhabditis elegans is characterized by widespread physiological and molecular changes, but the mechanisms that determine the rate at which these changes occur are not well understood. In this study, we identify a novel link between reproductive aging and somatic aging in C. elegans. By measuring global age-related changes in the proteome, we identify a previously uncharacterized group of secreted proteins in the adult uterus that dramatically increase in abundance with age. This accumulation is blunted in animals with an extended reproductive period and accelerated in sterile animals lacking a germline. Uterine proteins are not removed in old post-reproductive animals or in young vulvaless worms, indicating that egg-laying is necessary for their rapid removal in wild-type young animals. Together, these results suggest that age-induced infertility contributes to extracellular protein accumulation in the uterus with age. Finally, we show that knocking down multiple age-increased proteins simultaneously extends lifespan. These results provide a mechanistic example of how the cessation of reproduction contributes to detrimental changes in the soma, and demonstrate how the timing of reproductive decline can influence the rate of aging.
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spelling doaj-art-f2cceb05cbdb4088bf3ded3d062efe9a2025-08-20T03:11:01ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-12-011112e100572510.1371/journal.pgen.1005725Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.Stephanie M ZimmermanIzumi V HinksonJoshua E EliasStuart K KimAging in Caenorhabditis elegans is characterized by widespread physiological and molecular changes, but the mechanisms that determine the rate at which these changes occur are not well understood. In this study, we identify a novel link between reproductive aging and somatic aging in C. elegans. By measuring global age-related changes in the proteome, we identify a previously uncharacterized group of secreted proteins in the adult uterus that dramatically increase in abundance with age. This accumulation is blunted in animals with an extended reproductive period and accelerated in sterile animals lacking a germline. Uterine proteins are not removed in old post-reproductive animals or in young vulvaless worms, indicating that egg-laying is necessary for their rapid removal in wild-type young animals. Together, these results suggest that age-induced infertility contributes to extracellular protein accumulation in the uterus with age. Finally, we show that knocking down multiple age-increased proteins simultaneously extends lifespan. These results provide a mechanistic example of how the cessation of reproduction contributes to detrimental changes in the soma, and demonstrate how the timing of reproductive decline can influence the rate of aging.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005725&type=printable
spellingShingle Stephanie M Zimmerman
Izumi V Hinkson
Joshua E Elias
Stuart K Kim
Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.
PLoS Genetics
title Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.
title_full Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.
title_fullStr Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.
title_full_unstemmed Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.
title_short Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.
title_sort reproductive aging drives protein accumulation in the uterus and limits lifespan in c elegans
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005725&type=printable
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