Sex-specific aging in animals: Perspective and future directions

Abstract

Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age-associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer-lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or linked to other well-characterized processes. In particular, understanding the role of sex-determination mechanisms and sex differences in aging is relatively understudied. Here, we take a comparative, interdisciplinary approach to explore various hypotheses about how sex differences in aging arise. We discuss genomic, morphological, and environmental differences between the sexes and how these relate to sex differences in aging. Finally, we present some suggestions for future research in this area and provide recommendations for promising experimental designs.

Keywords: aging; comparative biology; lifespan; mortality; sex differences.

FIGURE 1

Sex‐specific age structure of adult wild baboons (Papio cynocephalus) and painted turtles (Chrysemys picta). Data from Bronikowski et al. 2011 and Bronikowski et al. 2021, respectively. In both populations, the male distributions are left‐skewed relative to the female distributions, and females have right extended distributions. The intensity of selection acting against a mutation that decreases age‐specific survival declines more rapidly with age for males in both species. Baboons have genotypic sex determination (degenerate sex chromosome in males). Painted turtles have environmental (temperature) sex determination (no sex chromosomes).

FIGURE 2

Sex differences in lifespan vary widely across animal taxa. Gray and black bars represent lifespan in females and males. Humans are an example of a species where females live longer, while in Brandt's bat, males live longer. See text for more examples. The curve illustrates that sex differences in lifespan (absolute value of lifespan(f)—lifespan(m)) form a continuum, from males living longer shown (left) to females living longer (right)

FIGURE 3

Variability in female age bias at sexual maturity across chordates. Female age bias is defined as female maturation age divided by the mean maturation age of both sexes. This distribution is centered at 1 (i.e., no age bias), with range from 0.42 to 1.62, with equal tails. Data from AnAge (birds contribute 48% of the data, mammals 40%)

FIGURE 4

Example taxonomic groups for comparative studies of aging. Species with diverse sex determining mechanisms include those with heterogametic sex chromosomes, non‐differentiated sex chromosomes, and environmental sex determination (warm temperature‐dependent female determination highlighted here; various forms of TSD are found in many reptiles). Species with contrasting patterns of sex‐specific lifespan include species with male‐biased, female‐biased, and unbiased lifespan. And species with inter‐ and intra‐specific variation in aging include diverse wild population and laboratory model species

FIGURE 5

Example study design focused on genome stability changes with advancing age. i) First select a species that has sex‐specific variation in demographic rate‐of‐aging (e.g., females live longer and age slower than males as pictured here for yellow baboons, Bronikowski et al. 2016). ii) Measure age‐related accessible (eu)chromatin and iii) concomitant gene expression. iv) Measure additional age‐related features of the epigenome. v) include functional assays of genome stability such as DNA repair efficiency. These genomic, epigenomic, and functional data can be integrated in deep learning pipelines to develop multi‐variate indices of sex‐and‐age specific change