Blocking IL-11 Keeps Aging Ovaries Soft and Extends Fertility in Mice

Researchers at Huazhong University of Science and Technology identified interleukin-11 (IL-11) as a key factor that increases the stiffness of the ovarian extracellular matrix—a change linked to reduced egg quality and the onset of menopause. The study, published in *Nature Aging*, reports that “the increase in ovarian matrix stiffness is critically dependent on IL-11.”

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Human ovarian tissue from three age groups (18–28, 35–42, and 47–52 years) and from patients with chemotherapy-induced premature ovarian insufficiency, polyendocrine metabolic ovarian syndrome, or ovarian endometriosis showed higher IL-11 expression in older and diseased samples. The authors note that “aging, chemotherapy, PCOS, and endometriosis all lead to the secretion of IL-11 in the ovaries, causing an increase in matrix stiffness.”

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The team first deleted the Il11 gene in mice, then applied RNA-loaded nanoparticles to suppress IL-11 signaling. Both approaches reduced ovarian collagen accumulation, lowered matrix stiffness, and increased the number of pups per pregnancy. The authors summarize that “blocking the IL-11 pathway can reduce the ovarian matrix stiffness and improve ovarian function in aging individuals, as well as in the presence of various pathological mediators.”

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While anti-IL-11 drugs are already in clinical trials for other conditions, researchers suggest repurposing them for reproductive health. Biomedical researcher Stuart Cook, not involved in the study, writes that “perhaps anti-IL-11 therapy may be trialed to prevent chemotherapy-induced premature ovarian insufficiency and/or to treat polycystic ovary syndrome.” The study authors conclude that “blocking IL-11 signaling in both physiological ovarian aging model and various pathological ovarian dysfunction models holds significant therapeutic potential for improving ovarian function.”

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• “The increase in ovarian matrix stiffness is critically dependent on IL-11," the study's authors explain in their paper, published in Nature Aging.” — Study authors, *Nature Aging*

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• “Notably, blocking the IL-11 pathway can reduce the ovarian matrix stiffness and improve ovarian function in aging individuals, as well as in the presence of various pathological mediators, indicating that this common cellular program can be triggered in response to ovarian injury from diverse causes.” — Study authors, *Nature Aging*

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• “We found that aging, chemotherapy, PCOS, and endometriosis all lead to the secretion of IL-11 in the ovaries, causing an increase in matrix stiffness,” — Study authors, *Nature Aging*

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• “frameborder="0´´ allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share" referrerpolicy="strict-origin-when-cross-origin" allowfullscreen> "Perhaps anti-IL-11 therapy may be trialed to prevent chemotherapy-induced premature ovarian insufficiency and/or to treat polycystic ovary syndrome," writes biomedical researcher Stuart Cook, who was not involved in the study, in an accompanying News & Views article for Nature.” — Stuart Cook, biomedical researcher

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• “Blocking IL-11 signaling in both physiological ovarian aging model and various pathological ovarian dysfunction models holds significant therapeutic potential for improving ovarian function," the study authors write.” — Study authors, *Nature Aging*

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