Sex Differences in Frailty.

Although women live longer lives than men, they tend to have poorer health status. Here, we review the biological and socio-behavioral factors that may contribute to this sex-frailty paradox. The conceptual framework that frailty is a product of the environment and the recovery rate provides a new understanding of women's frailty burden. Even developed countries may present an environment more adverse for women, and lifestyle factors may increase women's vulnerability to stochastic subcellular events that increase recovery time. The frailty index does not reach the theoretical maximal value of 1; its limit is lower in men (0.61) compared to women (0.69). Perhaps deterministic characteristics omitted in current deficit counts, such as reduced emotional adaptability, are more prevalent in men. Alternatively, different limits may result from quantitative evolutionary design, such as a fitness-frailty pleiotropy in men or fertility-frailty pleiotropy in women. The engineering principle of safety factors (maximal capacity divided by routine functioning) may also be informative. If the human system has the same safety factor as its organs (approximately 2.5), men may be 'calibrated' around a frailty index of 0.244, compared to 0.276 for women. Because 0.25 represents the tipping point between functional independence and reliance on others, evolutionary design may have allowed for some limited dependence in women, perhaps motivated by the perinatal period.