Widespread sex-dimorphism in aging and age-related diseases

Abstract

Although aging is a conserved phenomenon across evolutionary distant species, aspects of the aging process have been found to differ between males and females of the same species. Indeed, observations across mammalian studies have revealed the existence of longevity and health disparities between sexes, including in humans ( i.e. with a female or male advantage). However, the underlying mechanisms for these sex differences in health and lifespan remain poorly understood, and it is unclear which aspects of this dimorphism stem from hormonal differences ( i.e. predominance of estrogens vs. androgens) or from karyotypic differences ( i.e. XX vs. XY sex chromosome complement). In this review, we discuss the state of the knowledge in terms of sex-dimorphism in various aspects of aging, and in human age-related diseases. Where the interplay between sex differences and age-related differences has not been explored fully, we present the state of the field, to highlight important future research directions. We also discuss various dietary, drug or genetic interventions that were shown to improve longevity in a sex-dimorphic fashion. Finally, emerging tools and models that can be leveraged to decipher the mechanisms underlying sex differences in aging are also briefly discussed.