Abstract
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.
Highlights
Aging in C. elegans is characterized by stereotyped physiological changes over the course of its three week lifespan
To understand the process of aging at the molecular level in C. elegans, we measured changes in protein abundance with age, determined whether these age-related protein changes lead to dysfunction in old animals, and have elucidated one of the upstream pathways responsible for these aging changes
When the reproductive period ends, the removal of uterine proteins stops, causing them to accumulate to toxic levels
Summary
Aging in C. elegans is characterized by stereotyped physiological changes over the course of its three week lifespan. Other tissues overproliferate with age; for example, aged worms have increased cuticle thickness, accumulation of yolk protein in the body cavity, masses in the germline, and ectopic neuronal branching [3,4,5,6]. Transciptional profiling has been used to identify genes that change expression during C. elegans aging at the RNA level [7,8,9]. This has allowed the identification of transcription factors that bind and regulate these age-regulated genes. The mechanisms that induce changes in transcription factor expression, and determine the rate and timing of their change, are generally not known
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