Vitellogenin accumulation leads to reproductive senescence by impairing lysosomal function

The maintenance of proteostasis is essential for cellular and organism healthspan. How proteostasis collapse influences reproductive span remains largely unclear. In Caenorhabditis elegans, excess accumulation of vitellogenins, the major components in yolk proteins, is crucial for the development of the embryo and occurs throughout the whole body during the aging process. Here, we show that vitellogenin accumulation leads to reproduction cessation. Excess vitellogenin is accumulated in the intestine and transported into the germline, impairing lysosomal activity in these tissues. The lysosomal function in the germline is required for reproductive span by maintaining oocyte quality. In contrast, autophagy and sperm depletion are not involved in vitellogenin accumulation-induced reproductive aging. Our findings provide insights into how proteome imbalance has an impact on reproductive aging and imply that improvement of lysosomal function is an effective approach for mid-life intervention for maintaining reproductive health in mammals.

Automated summary

The maintenance of proteostasis is crucial for cellular and organism healthspan, yet the impact of proteostasis collapse on reproductive span is not fully understood. In Caenorhabditis elegans, excess accumulation of vitellogenins, major components in yolk proteins, is vital for embryonic development and occurs during the aging process. Our study reveals that vitellogenin accumulation leads to reproductive cessation by impairing lysosomal activity in the intestine and germline. Lysosomal function in the germline is necessary for reproductive span by maintaining oocyte quality. Autophagy and sperm depletion are not involved in vitellogenin accumulation-induced reproductive aging. These findings provide insights into the influence of proteome imbalance on reproductive aging and suggest that improving lysosomal function could be an effective intervention for maintaining reproductive health in mammals.