Plasma Proteomic Signature of Cellular Senescence and Markers of Biological Aging Among Postmenopausal Women

Abstract

We aimed to investigate the association of circulatory senescence-associated secretory phenotypes (SASPs) produced by senescent cells with chronological and menopausal age in women aged 45 years or more. The proteomic profiles for 32 SASP factors of plasma samples were measured in 76 healthy postmenopausal women aged 46-82 years from the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study (KoGES-CAVAS). We assessed the association between the SASP factors and aging indicators (chronological age, menopausal age, and years since menopause) using single- and multiprotein models. First, we composed a profile of proteins associated with chronological age, menopausal age, and years since menopause. In a single-protein model, three proteins (growth differentiation factor 15 [GDF15], insulin-like growth factor binding protein-2 [IGFBP-2], and tumor necrosis factor-alpha [TNF-alpha]) are positively associated with chronological age. Menopausal age and years since menopause are interrelated with interleukin-8 (IL-8). The direction of association between menopausal age and monocyte chemoattractant protein-1 (MCP-1) was only negative, and IGFBP-2 and TNF-alpha were significant in all three aging factors. We also constructed parsimonious multiprotein models to confirm the association of the proteomic signature for aging after adjusting for covariates and the combination of proteomic signature of 13 proteins (GDF15, interferon-gamma [IFN-gamma], IGFBP-2, IGFBP-7, IL-15, IL-1 beta, IL-17A, IL-8, MCP-1, tissue inhibitors of metalloproteinase-2 [TIMP-2], TNF-alpha, vascular endothelial growth factor-A [VEGF-A], and interferon-inducible protein 10 [IP-10]) appear to be associated with chronological age and menopausal state of individuals. Thus, by observing association between the selected SASPs and age-related markers among healthy postmenopausal women, we examine how menopause in women relates to proteomic indicators of aging and highlight the potential use of SASP factors as a marker to reflect the state of biological aging attributed by ovarian senescence.