Declining ribosome function limits oocyte longevity
- 1University of British Columbia
Abstract
Protein synthesis declines with age across many tissues, but whether this decline actively contributes to physiological aging remains unclear. Oocytes may be particularly vulnerable because they rely on ribosomes synthesized during growth and maintained for prolonged periods without continual replacement. Here we show that declining translational capacity is a causal component of oocyte aging. An unbiased genetic screen identified ribosome dosage as a major determinant of oocyte longevity, and experimentally reducing ribosome abundance was sufficient to accelerate the loss of developmental competence and prematurely recapitulate meiotic defects that arise during natural aging, while also producing defects in early embryonic development. Ribosomes isolated from aged Drosophila oocytes exhibit ~50% lower translational activity despite only a modest reduction in ribosome abundance and preserved gross structure and composition, with both ribosomal subunits contributing to this functional decline. Protein synthesis also declines markedly in aged metaphase-I mouse oocytes. Together, these findings identify long-lived translational machinery as an intrinsic vulnerability of the oocyte and establish declining ribosome function as a mechanistic contributor to reproductive aging.
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BibTeX
@misc{judson2026declining,
title = {{Declining ribosome function limits oocyte longevity}},
author = {K. L. Judson and K. J. Danielson and S. Tang and S. Chandhok and E. Hui and F. Wong and T. Mayor and K. Schindler and E. Greenblatt},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755503},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755503v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Declining ribosome function limits oocyte longevity
AU - K. L. Judson
AU - K. J. Danielson
AU - S. Tang
AU - S. Chandhok
AU - E. Hui
AU - F. Wong
AU - T. Mayor
AU - K. Schindler
AU - E. Greenblatt
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755503
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755503v1
AB - Protein synthesis declines with age across many tissues, but whether this decline actively contributes to physiological aging remains unclear. Oocytes may be particularly vulnerable because they rely on ribosomes synthesized during growth and maintained for prolonged periods without continual replacement. Here we show that declining translational capacity is a causal component of oocyte aging. An unbiased genetic screen identified ribosome dosage as a major determinant of oocyte longevity, and experimentally reducing ribosome abundance was sufficient to accelerate the loss of developmental competence and prematurely recapitulate meiotic defects that arise during natural aging, while also producing defects in early embryonic development. Ribosomes isolated from aged Drosophila oocytes exhibit ~50% lower translational activity despite only a modest reduction in ribosome abundance and preserved gross structure and composition, with both ribosomal subunits contributing to this functional decline. Protein synthesis also declines markedly in aged metaphase-I mouse oocytes. Together, these findings identify long-lived translational machinery as an intrinsic vulnerability of the oocyte and establish declining ribosome function as a mechanistic contributor to reproductive aging.
ER -