Studying Ovaries to Understand How We All Age

Amazing stuff!

"Ovaries are the fastest aging organ in the body, but the least studied organ in aging research.

The impact of aging ovaries on a woman’s fertility are well known, but aging ovaries—which shrink from the size of a kiwi to a kidney bean—also have much wider impacts on a woman’s health in the later decades of life. The earlier the ovaries age, the more likely a woman is to develop heart disease, dementia, depression, glaucoma, and other diseases, and die earlier.

“The ovary is an endocrine organ and influences aging in the entire body ...

“By delaying ovarian aging, we could live longer and healthier lives,” she says. ...

In our latest research, we compared ovaries in women in their 20s versus 40s or 50s, and the big surprise was that there’s nothing special about how ovaries age. The same genetic programs and molecular signals you see in an old brain or heart or kidney in your 60s, you see in this tiny organ in your 40s.

The good news is that means geroprotective drugs, which delay aging in animals, could be used to delay aging in the ovary. ..."

From the 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."

Studying Ovaries to Understand How We All Age | Columbia University Irving Medical Center "New findings from Columbia's Yousin Suh suggests ovarian aging has lessons for us all."

Molecular and genetic insights into human ovarian aging from single-nuclei multi-omics analyses (open access)

Fig. 2: Aging alters ovarian cellular composition and affects the transcriptional activity of pathways involved in the hallmarks of aging across cell types.