A protein stiffens ovaries and drives aging

The connective tissue layer inside the ovary, known as the stroma, becomes progressively stiffer with age. This stiffening impairs follicle development and disrupts hormonal balance. The cause has remained unclear until now. The study, published in Nature Aging, identifies a specific culprit: the protein interleukin-11 (IL-11).

IL-11 is a signalling molecule involved in inflammation and connective tissue formation. The researchers found that IL-11 levels rise in the ovaries of ageing mice, rats and humans. Elevated IL-11 activates fibroblasts, the cells responsible for producing extracellular matrix, causing them to secrete excess structural material. This accumulation makes the surrounding tissue increasingly rigid.

Stiff tissue impairs fertility

The mechanical consequences are significant. Follicles embedded in hardened stroma develop less effectively, and hormone levels become unbalanced. In aged mice, inhibiting IL-11 improved ovarian function, restored hormonal balance and increased fertility. These are preliminary results from animal models, but the parallels with human tissue are notable: IL-11 also rises in older human ovaries.

A broader pattern in organ aging

IL-11 has already attracted attention as a potential therapeutic target in cardiac and liver fibrosis. This study adds another organ to that list. From a longevity perspective, if IL-11-driven tissue stiffening is a recurring pattern across ageing organs, inhibitors of this protein could potentially address multiple tissue types simultaneously. The researchers stress that clinical applications remain distant and that further studies are needed to establish safety and efficacy in humans.

The findings reframe ovarian ageing: it is not only a hormonal process but also a mechanical one. Tissue stiffness plays an active role in declining reproductive function, independent of hormone levels.

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