Associations of biomarkers of cellular senescence with physical and cognitive function among older women with or without a history of premenopausal bilateral oophorectomy.

OBJECTIVES

To study whether a history of premenopausal bilateral oophorectomy (PBO) may influence circulating concentrations of cellular senescence biomarkers and their associations with measures of physical and cognitive function later in life.

STUDY

DESIGN

The plasma concentrations of 29 candidate senescence biomarkers and parameters of physical and cognitive function were measured in 510 older women, comprising 273 with a history of PBO and 237 referents.

MAIN OUTCOME MEASURES: Plasma concentrations of senescence biomarkers and their associations with measures of physical and cognitive function.

RESULTS

In participants with a history of PBO compared to referents, only the plasma levels of tumor necrosis factor alpha (TNFα) and tumor necrosis factor receptor 2 (TNFR2) were statistically significantly higher than they were in the referent group, whereas matrix metalloproteinase 2 (MMP2) was lower. Overall, measures of physical and cognitive function did not differ between those with and without PBO. In an exploratory analysis, several senescence-related biomarkers were associated with chronological age, body mass index, and measures of physical function, including 6-minute walk distance and muscle strength and power. Only few biomarkers were associated with measures of cognitive function. Using machine learning, subsets of biomarkers in combination with demographic and clinical covariates exhibited higher value than the covariates alone in predicting most of the physical and cognitive function outcomes in cross-sectional analyses.

CONCLUSIONS

The circulating concentrations of several candidate senescence biomarkers were associated with physical and cognitive function in a cohort of older women, but only a few biomarkers differed between participants with a history of PBO and referents. Additional research is needed to better understand the influence of PBO on the biology of aging.