2024-12-16 コロンビア大学
<関連情報>
- https://www.cuimc.columbia.edu/news/studying-ovaries-understand-how-we-all-age
- https://www.nature.com/articles/s43587-024-00762-5
ヒト卵巣の老化に関する分子的・遺伝学的洞察を単一核マルチオミクス解析から得る Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses
Chen Jin,Xizhe Wang,Jiping Yang,Seungsoo Kim,Adam D. Hudgins,Amir Gamliel,Mingzhuo Pei,Daniela Contreras,Melody Devos,Qinghua Guo,Jan Vijg,Marco Conti,Jan Hoeijmakers,Judith Campisi,Rogerio Lobo,Zev Williams,Michael G. Rosenfeld & Yousin Suh
Nature Aging Published:22 November 2024
DOI:https://doi.org/10.1038/s43587-024-00762-5
Abstract
The ovary is the first organ to age in the human body, affecting both fertility and overall health. However, the biological mechanisms underlying human ovarian aging remain poorly understood. Here we present a comprehensive single-nuclei multi-omics atlas of four young (ages 23–29 years) and four reproductively aged (ages 49–54 years) human ovaries. Our analyses reveal coordinated changes in transcriptomes and chromatin accessibilities across cell types in the ovary during aging, notably mTOR signaling being a prominent ovary-specific aging pathway. Cell-type-specific regulatory networks reveal enhanced activity of the transcription factor CEBPD across cell types in the aged ovary. Integration of our multi-omics data with genetic variants associated with age at natural menopause demonstrates a global impact of functional variants on gene regulatory networks across ovarian cell types. We nominate functional non-coding regulatory variants, their target genes and ovarian cell types and regulatory mechanisms. This atlas provides a valuable resource for understanding the cellular, molecular and genetic basis of human ovarian aging.
