Scholarlink

Background <p>Ovarian aging, marked by the gradual decline in both the number and quality of oocytes, significantly impacts women's reproductive lifespan and overall health. However, the biological mechanisms driving ovarian aging remain poorly understood and current treatment strategies are limited.</p> Results <p>We perform an integrative analysis using multi-omics summary data and genome-wide association studies for ovarian aging to identify molecular traits linked to ovarian aging. By applying Mendelian randomization and cross-omics association approaches, we prioritize key proteins, gene expressions, splicing events, and metabolites. Our analysis identifies conservation of key genes across species and cell types, with the mismatch repair gene MSH6 (MutS Homolog 6) emerging as a consistently prioritized candidate. Experimental validation shows that targeting DNA repair through PD-L1 (Programmed Death-Ligand 1) blockade may offer a potential therapeutic strategy to delay ovarian aging.</p> Conclusions <p>This study uncovers the multi-layered genetic and molecular architecture underlying ovarian aging. The identified molecular traits provide promising candidates for functional studies and suggest new avenues for developing therapies aimed at preserving ovarian function and preventing age-related decline.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Multi-omics pleiotropic association analyses reveal functionally relevant genes and druggable pathways for ovarian aging

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月28日

查看全文
  • Xuan Lian,
  • Shuang Song,
  • Chen Lou,
  • Ming Zhu,
  • Yan Li,
  • Wenjian Li,
  • Xintong Jiang,
  • Guiquan Wang,
  • Haiyan Yang,
  • Lin Wang,
  • Liying He,
  • Yunlong Ma,
  • Xi Dong,
  • Yijie Chen,
  • Hsun-Ming Chang,
  • Wencheng Zhu,
  • Jia Wang,
  • Yang Yu,
  • Yang Wu,
  • Yue Zhao,
  • Liangshan Mu

摘要

Background

Ovarian aging, marked by the gradual decline in both the number and quality of oocytes, significantly impacts women's reproductive lifespan and overall health. However, the biological mechanisms driving ovarian aging remain poorly understood and current treatment strategies are limited.

Results

We perform an integrative analysis using multi-omics summary data and genome-wide association studies for ovarian aging to identify molecular traits linked to ovarian aging. By applying Mendelian randomization and cross-omics association approaches, we prioritize key proteins, gene expressions, splicing events, and metabolites. Our analysis identifies conservation of key genes across species and cell types, with the mismatch repair gene MSH6 (MutS Homolog 6) emerging as a consistently prioritized candidate. Experimental validation shows that targeting DNA repair through PD-L1 (Programmed Death-Ligand 1) blockade may offer a potential therapeutic strategy to delay ovarian aging.

Conclusions

This study uncovers the multi-layered genetic and molecular architecture underlying ovarian aging. The identified molecular traits provide promising candidates for functional studies and suggest new avenues for developing therapies aimed at preserving ovarian function and preventing age-related decline.