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Vitellogenin accumulation leads to reproductive senescence by impairing lysosomal function

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Abstract

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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (U1802233) and the Major Science and Technology Project in Yunnan Province of China (202001BB050001). We are grateful to Dr. J Xu (McMaster University, Canada) for their critical reading of this manuscript. We thank the Caenorhabditis Genetics Center, and Drs. G Ruvkun, M Dong, and X Wang for nematode strains.

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Authors and Affiliations

  1. Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, 650091, China

    Jie Tang, Yi-Cheng Ma, Yuan-Li Chen, Rui-Qiu Yang, Heng-Chen Liu, Xin Wang, Cheng-Gang Zou & Ke-Qin Zhang

  2. Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College (CAMS & PUMC), Kunming, 650118, China

    Jie Tang

  3. Faculty of Basic Medicine, Kunming Medical University, Kunming, 650500, China

    Yuan-Li Chen

  4. Institute of Biology and Environmental Engineering, School of Chemistry, Biology & Environment, Yuxi Normal University, Yuxi, 653100, China

    Baosen Ni

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  1. Jie Tang
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Tang, J., Ma, YC., Chen, YL. et al. Vitellogenin accumulation leads to reproductive senescence by impairing lysosomal function. Sci. China Life Sci. 66, 439–452 (2023). https://doi.org/10.1007/s11427-022-2242-8

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