The ovaries, often considered inactive after menopause, may still shape how women age, with human tissues revealing inflammatory changes and molecular similarities to ovarian cancer.
The ovaries continue to change for decades after menopause, long after their role in reproduction has ended. In a study of ovarian tissue from 28 women aged 50 to 75, scientists found age-related changes in proteins associated with inflammation, immune activity and the structure of tissues surrounding cells.
The research, conducted by scientists at Northwestern University and the Buck Institute for Research on Aging, was published in Aging cell.
“In the ovary, we reach a point of no return with regard to fertility in which it no longer produces eggs, and I would venture to say that most people assume that those ovaries just sit there, doing nothing, like the appendix,” said co-corresponding author Francesca Duncan, associate professor of reproductive sciences in medicine at Northwestern University’s Feinberg School of Medicine. “But that’s what makes this study very different.”
Older ovaries show an inflammatory change
To study changes after menopause, researchers looked beyond ovarian hormones to examine the protein composition of tissues. Co-corresponding author Birgit Schilling, professor and director of the Buck Institute Mass Spectrometry Center, led the team responsible for this analysis. Led by Mark Watson, a Buck Institute scientist and member of the Schilling lab, the work used advanced proteomic technologies capable of identifying and measuring thousands of proteins at once. The researchers analyzed 5,812 groups of proteins in normal ovarian tissue.
Human ovarian tissue is difficult to obtain, making the collection of 28 ovaries extremely valuable, Duncan said. Focusing on an age range of 25 years after menopause allowed the team to isolate differences within the postmenopausal years, rather than comparing young and old ovaries over a lifetime. The technology also made it possible to examine thousands of proteins in each sample.
“When we analyzed the data in several different statistical ways, what became clear across all of these methodologies was that the ovary was not stagnating,” Schilling said. “Actually, over the decades, there have been some pretty dramatic differences in terms of increasing levels of certain proteins with age and decreasing certain protein levels, which tells us that this organ is quite dynamic.”
The ovaries of younger postmenopausal women contained more proteins involved in maintaining the structure of cells and tissues. Older ovaries contained more proteins associated with inflammation, immune activity, and the breakdown and rebuilding of tissue around cells. The differences were greater between women in their 50s and those aged 70 and over.
Some molecular patterns also resembled those observed in cellular senescence. In this state, aging or damaged cells stop dividing but remain biologically active and can send signals that affect nearby tissues.
“Our data indicate progressive aging characteristics in which the ovary appears to lose its original identity and ends up doing something different,” Duncan said. “We don’t yet know if there is a point in a woman’s life when this organ is no longer beneficial and if it is actually harmful. These results really highlight the need to ask that question.”
Similar remodeling in mice and women
Duncan’s group had previously found similar evidence of continued remodeling in the ovaries of postmenopausal mice. She began both this research and the human study with expectations that the results ultimately challenged.
“I predicted that if we took a 50-year-old ovary, a 60-year-old ovary, a 70-year-old ovary, an 80-year-old ovary, they would all look exactly the same, have no eggs and be basically non-functional,” Duncan said. “The fact that we are seeing this in all species gives us confidence that this is not just a random event, but that something truly significant is happening in biology.”
Women now routinely live decades after menopause, Duncan noted, making the role of the ovary during this long period increasingly relevant to understanding women’s health beyond fertility.
“The ovary is not just a reproductive organ,” Schilling said. “It really influences how a person ages because it speaks to all these other organs, like the brain, but also the bones, and women after menopause often experience a lot of bone problems. So we think there’s a connection between all these organs.”
Cancer-related proteins in cancer-free ovaries
Changes in tissue structure also link the new findings to an earlier question about ovarian cancer. In 2016, Duncan’s lab was the first to discover that aging ovaries become increasingly inflamed, fibrous and stiff, resembling scars in other tissues. Cancer cells can grow in stiff, collagen-rich environments, prompting researchers to investigate whether these changes could make older ovaries more hospitable to cancer cells. The new protein analysis provides molecular insight into this remodeling process after menopause.
All tissues in the present study appeared normal and cancer-free. Nonetheless, some proteins previously associated with ovarian cancer were more abundant in aging ovaries, with the strongest signal seen in women in their 60s. This does not mean that the ovaries were cancerous or precancerous. This suggests that healthy ovarian aging and ovarian cancer share certain biological processes.
“It’s not that all postmenopausal women get ovarian cancer, but we know that this fibrous inflammatory environment is certainly an environment in which cancer cells prefer to concentrate,” Duncan said. “All of this is consistent with the idea that ovarian aging is a potential third impact of ovarian cancer, with the first impact being genetic and the second impact being environmental. So can we therapeutically target the aging ovary to reduce the risk of ovarian cancer, or can we develop new biomarkers for ovarian cancer?”
The question of whether aging of the ovary can lead to changes elsewhere in the body remains open.
“Is the ovary the canary in the coal mine in women?” said Duncan, who is also an associate professor in residence at the Buck Institute. “Could aging of the ovary trigger a cascade of changes that continue throughout the body as women age?
The results do not allow us to know whether healthy ovaries should be removed after menopause, the researchers emphasize. Much more research is needed to determine exactly what the organ is doing during these years and whether the observed changes contribute to chronic disease or are simply features of normal aging.
Reference: “The human ovary exhibits dynamic molecular remodeling during postmenopausal decades” by Mark A. Watson, Bikem Soygur, Christina D. King, Pooja R. Devrukhkar, Simon Melov, Elisheva D. Shanes, Mary Ellen G. Pavone, Francesca E. Duncan and Birgit Schilling, September 7, 2026, Aging cell.
DOI: 10.1111/acel.70714
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