Inflammaging and the sex-frailty paradox

Background: The “sex-frailty paradox” is a concept that indicates how women despite being more frail are less susceptible to death than men. The roots of this paradox may lie in the different combination of biological, behavioural, and social factors between the two sexes. The aim of this study is to deepen our understanding of the different biological mechanisms underlying frailty and longevity in men and women, thus shedding further light on the sex-frailty paradox. Methods: We studied 452 subjects (315 women and 137 men) stratifying them by age (≤ 80, 81–99 and ≥ 100 years) and sex. A 47-item frailty index was calculated. Plasma concentrations of inflammatory markers were analysed by next-generation ELISA. Results: Women aged ≤ 80 years were less frail while those aged ≥ 100 years were more frail than their male counterparts. Interestingly, the 81-99-year-old group showed similar frailty degree between females and males. Most of the biomarkers increased with age in both sexes, while being associated differently with frailty, indicating that there are specific biological roots in the two sexes that influence frailty. Conclusions: Trying to delineate the unique molecular profile of older women and men becomes essential for understanding the mechanisms underlying the sex-frailty paradox. Further research on sex-specific determinants is required to enhance our understanding of aging and develop effective strategies to promote health and longevity in both sexes.