Experimental gerontologySep 30, 2025

Effects of aging skin cells' secretions on the spread of ovarian cancer

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 19, 2026

Abstract

Over 50% of ovarian cancer cases occur in women aged 65 and older.

Senescent ovarian fibroblasts showed increased levels of intracellular Fibronectin and impaired assembly of this protein into the extracellular matrix.
The structure of the extracellular matrix was significantly altered in senescent ovarian fibroblasts.
The secretome from senescent fibroblasts was characterized by a pro-inflammatory profile with immune-modulatory cytokines.
Exposure to the senescent fibroblast secretome did not impact ovarian cancer cell proliferation but increased resistance to cell death.
Senescent fibroblasts significantly enhanced the migration and invasion of ovarian cancer cells.
These findings suggest that age-related changes in the tumor microenvironment may support cancer progression.

Simplified

Aging is a significant risk factor in ovarian cancers, which remains one of the most lethal gynecological malignancies. Over 50 % of ovarian cancer cases occur in women aged 65 and older. During aging, senescent cells progressively accumulate in various tissues, contributing to structural and inflammatory changes in the tumor microenvironment. While recent studies have underscored the role of the senescent mesothelial cells in facilitating cancer cell dissemination, the contribution of senescent fibroblasts that are a major component of the connective tissue, remains elusive. In this study, we first characterized the senescent phenotype of human ovarian fibroblasts, with a focus on extracellular matrix (ECM) remodeling and the senescence-associated secretory phenotype (SASP). Senescent ovarian fibroblasts exhibited an accumulation of intracellular Fibronectin (Fn), impaired fibrillar Fn into ECM assembly, and marked alterations in ECM organization. SASP profiling revealed a pro-inflammatory secretome enriched in immune-modulatory cytokines and factors potentially involved in cancer cell dissemination and metastasis. We then evaluated the influence of the senescent fibroblast secretome on ovarian cancer cell behavior. While it did not alter cancer cell proliferation, it conferred resistance to apoptosis and significantly enhanced cancer cell migration and invasion. Altogether, our findings highlight the role of senescent ovarian fibroblasts in promoting cancer cell dissemination and suggest that age-related stromal changes contribute to disease progression.

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Declaration of competing interest The authors declare that there is no conflict of interest.

PubMed

Effects of aging skin cells' secretions on the spread of ovarian cancer

Abstract

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Competing interests

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Abstract

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