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Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
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Ribosome dysregulation and intervention in age-related infertility.
Jie Li1, Honghong Wang2, Pengfei Zhu2
1State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Department of Cell Biology and Genetics, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Cell Reports. Medicine
|October 28, 2025
Summary
Female fertility declines with age due to molecular changes in eggs and cumulus cells. Ribosome gene transcription increases, but rapamycin treatment shows promise for improving pregnancy outcomes in older women.
Area of Science:
- Reproductive Biology
- Molecular Genetics
- Gerontology
Background:
- Female fertility naturally declines with advancing age.
- The molecular mechanisms underlying age-related infertility are not fully understood.
- Unexplained infertility in older women presents a significant clinical challenge.
Purpose of the Study:
- To investigate the molecular basis of age-related infertility in women.
- To identify specific cellular and molecular changes in oocytes and cumulus cells associated with aging.
- To evaluate the therapeutic potential of rapamycin in treating age-related infertility.
Main Methods:
- Transcriptome analysis of oocytes and cumulus cells from women in their mid-thirties.
- Analysis of gene expression related to meiosis, protein homeostasis, and ribosome biogenesis.
- Assessment of DNA methylation and heterochromatin patterns.
- In vitro treatment with rapamycin and evaluation of its effects on cellular processes.
- Clinical application of rapamycin in patients undergoing in vitro fertilization (IVF).
Main Results:
- Increased transcription of ribosome genes observed in aging oocytes and cumulus cells.
- Downregulation of meiosis genes, actin, and cohesin components in aged oocytes.
- Disruption of lysosomes and proteostasis in aged cumulus cells.
- Link between DNA hypomethylation, altered heterochromatin, and increased ribosome gene transcription.
- Rapamycin treatment improved protein homeostasis and resulted in high-quality blastocysts and successful pregnancies in infertile patients.
Conclusions:
- Elevated ribosome gene transcription plays a causal role in age-related infertility.
- Disruptions in meiosis, proteostasis, and epigenetic regulation contribute to diminished fertility with age.
- Rapamycin is a promising therapeutic agent for improving pregnancy outcomes in women with age-related infertility and recurrent IVF failure.
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