Sex gap in aging and longevity: can sex chromosomes play a role?

Abstract

It is well known that women live longer than men. This gap is observed in most human populations and can even reach 10-15 years. In addition, most of the known super centenarians (i.e., humans who lived for > 110 years) are women. The differences in life expectancy between men and women are often attributed to cultural differences in common thinking. However, sex hormones seem to influence differences in the prevalence of diseases, in the magnitude of aging, and in the longevity between men and women. Moreover, far from being human specific, the sex gap in longevity is extremely common in non-human animals, especially in mammals. Biological factors clearly contribute to such a sex gap in aging and longevity. Different hypotheses have been proposed to explain why males and females age and die differently. The cost of sexual selection and sexual dimorphism has long been considered the best explanation for the observed sex gap in aging/longevity. However, the way mitochondria are transmitted (i.e., through females in most species) could have an effect, called the mother's curse. Recent data suggest that sex chromosomes may also contribute to the sex gap in aging/longevity through several potential mechanisms, including the unguarded X/Z, the toxic Y/W and the loss of Y/W. We discuss future research directions to test these ideas.

Keywords: Aging; Klinefelter; Longevity; Mother’s curse; Sex chromosomes; Sex hormones; Sexual dimorphism; Transposable elements; Turner.

Fig. 1

Graphical display of some mortality metrics mentioned in the article. a represents a standard age-specific mortality curve for a mammalian species. Mortality decreases from birth to early adulthood, then stays low and relatively constant (i.e., prime-age stage) and finally starts to increase. The age when mortality starts to increase is the age at the onset of senescence or aging, and the intensity of the increase in the mortality rate with age is defined by the rate of senescence or aging. Males and females can differ in longevity in various ways. For instance, males and females can differ in the annual adult mortality (b), the age at the onset of aging and (c) the rate of aging (d). We did not represent scenarios where more than one trait can differ between males and females (see Box 1 for a thorough definition of the mortality key terms)

Fig. 2

The contribution of sex chromosomes to sex-specific differences in longevity and possible mechanisms. a The relationship between either female-biased or male-biased adult sex ratios and the sex chromosome type in vertebrates (adapted from [99]). The mechanisms through which sex chromosomes can impact longevity: (b) the unguarded X effect, (c) the toxic Y effect and (d) the loss of Y chromosomes. See text for details