The ovaries keep changing after menopause, and protein analysis shows inflammation rising and the scaffold between cells being remodeled with age
The ovaries keep changing after menopause, and protein analysis shows inflammation rising and the scaffold between cells being remodeled with age
On October 13, the journal Aging Cell published a study by the Buck Institute for Research on Aging and Northwestern University. The researchers measured 5812 proteins in the ovaries of 28 women aged 50 to 75.
Francesca Duncan, one of the two corresponding authors, said this about postmenopausal ovaries in a press release:
"I would venture to say most people think these ovaries just sit there doing nothing, like an appendix."
Duncan herself expected the ovaries of women in their 50s, 60s and 70s to look the same and to be essentially nonfunctional. Earlier work had pointed the other way, however. In 2016 her lab showed in mice that collagen builds up with age in the stroma, the supporting tissue of the ovary, and that old animals develop giant cells formed from fused immune macrophages, a feature linked to chronic inflammation. In 2026 the same group found that after the end of fertility the genes active in mouse ovaries are mostly immune genes. In women, ovarian proteins had been measured mainly before menopause and around its onset, so the new study included only postmenopausal women.
The ovaries had been removed during gynecological surgery, and a pathologist had classified the tissue as normal. The women were split into three groups: 50 to 59 years (11 women), 60 to 69 (10), and 70 and older (7). Compared with the 50 to 59 group, women aged 60 to 69 differed by at least 1.5-fold in the levels of 40 proteins, and women aged 70 and older differed in 117. Women aged 50 to 59 had higher levels of proteins that handle RNA and regulate genes. Women aged 70 and older had higher levels of proteins involved in fat metabolism and in the inflammatory responses of innate immunity. These included complement, a cascade of proteins the immune system uses to mark targets for destruction.
The extracellular matrix, the network of proteins between cells, was also remodeled. Fibromodulin, which arranges collagen fibers and restrains the signal that triggers scarring, decreased with age, while TGM2, an enzyme that cross-links matrix proteins, increased. The authors read this pair of changes as a shift toward tissue that is more cross-linked and more prone to remodeling. Antibody staining of tissue sections confirmed the loss of fibromodulin in eight women.
Four methods of analysis identified 26 proteins that changed most consistently with age. A combined score based on these proteins, calculated on the same 28 samples, rose with age (correlation 0.84). Some of the proteins that increased, such as the signaling protein WNT4, are secreted by ovarian cells. The authors suggest that the postmenopausal ovary continues to take part in signaling within the tissue and possibly between organs.
Senescent cells, which have stopped dividing, also release inflammatory signals. Several proteins, including TGM2, changed with age in the same direction as they did in pieces of ovarian tissue in which senescence had been induced with the chemotherapy drug doxorubicin.
Cancer cells take hold more easily in dense, collagen-rich tissue. Duncan's lab is testing whether age-related changes make the ovary a favorable site for cancer cells. Of 35 proteins that the literature links to ovarian cancer, 21 were detected in the data, TGM2 among them. Their average level was higher in the ten women aged 60 to 69 than in the other participants. When the participants were randomly reshuffled between groups, a difference this large or larger appeared in 4.9% of cases. This decade includes the median age at diagnosis of ovarian cancer, which is 63. Duncan says the aging ovary may act as a "third hit" for this cancer, after a genetic factor and an environmental one. She puts the open question this way:
"We don't yet know whether there is ever a point in a woman's life when this organ stops being useful and actually becomes harmful."