Many taxa show substantial differences in lifespan between the sexes: however, these differences are not always in the same direction

The sex with the reduced sex chromosome dies earlier: a comparison across the tree of life. Zoe A. Xirocostas, Susan E. Everingham and Angela T. Moles. Biology Letters, March 4 2020. https://doi.org/10.1098/rsbl.2019.0867

Abstract: Many taxa show substantial differences in lifespan between the sexes. However, these differences are not always in the same direction. In mammals, females tend to live longer than males, while in birds, males tend to live longer than females. One possible explanation for these differences in lifespan is the unguarded X hypothesis, which suggests that the reduced or absent chromosome in the heterogametic sex (e.g. the Y chromosome in mammals and the W chromosome in birds) exposes recessive deleterious mutations on the other sex chromosome. While the unguarded X hypothesis is intuitively appealing, it had never been subject to a broad test. We compiled male and female longevity data for 229 species spanning 99 families, 38 orders and eight classes across the tree of life. Consistent with the unguarded X hypothesis, a meta-analysis showed that the homogametic sex, on average, lives 17.6% longer than the heterogametic sex. Surprisingly, we found substantial differences in lifespan dimorphism between female heterogametic species (in which the homogametic sex lives 7.1% longer) and male heterogametic species (in which the homogametic sex lives 20.9% longer). Our findings demonstrate the importance of considering chromosome morphology in addition to sexual selection and environment as potential drivers of sexual dimorphism, and advance our fundamental understanding of the mechanisms that shape an organism's lifespan.

4. Discussion

Our study provides evidence that, across multiple taxa, the heterogametic sex tends to have a considerably shorter lifespan than the homogametic sex. That is, an organism's chromosome morphology seems to have a substantial role in shaping this key life-history trait. The 17.6% difference between the lifespans of homogametic and heterogametic sexes revealed here is substantial enough to have major ecological and evolutionary implications. However, heterogametic sex chromosomes include everything from a complete absence of the second sex chromosome (X0 or Z0), to a highly reduced second sex chromosome (e.g. XY in humans), to X and Y or Z and W chromosomes of nearly equal length [5,32,33]. As not all heterogametic species have a degraded sex chromosome, our study likely represents a conservative test of the unguarded X hypothesis. A future direction will be to formally test the hypothesis that the difference in lifespan between sexes is proportional to the proportional difference in chromosome length between sexes. That is, to test the idea that species in which the second chromosome is absent or extremely reduced have a greater reduction in the lifespan of the heterogametic sex than do taxa in which the difference between sex chromosomes is relatively small. Ideally, this question should be addressed using a diverse range of taxa, both for generality, and to include species with as many different chromosome configurations, life histories and mating systems as possible. Another interesting direction for future research would be to begin to quantify the relative contributions of factors such as chromosome morphology, sexual selection, parental investment and exposure to predators.

Our second major finding was that when males are the heterogametic sex, they die 20.9% earlier than their female counterparts, but when females are the heterogametic sex, they die only 7.1% earlier than their male counterparts. Three possible explanations for this surprising trend include: (1) the degree of degradation of the Y chromosome, (2) telomere dynamics, and (3) side effects of sexual selection.

(1)	It is possible that the Y chromosome in male heterogametic species might tend to be more degraded than the W chromosome in female heterogametic species, potentially leading to a difference in heterogametic lifespan between XY and ZW systems. We know that many mammals (including humans) have highly reduced Y chromosomes [33–35]. There is also evidence that the relative length of the W and Z chromosomes can vary substantially even within clades (e.g. birds, snakes; [6,36–39]). However, a comparative analysis of the degradation of chromosomes across the tree of life has not yet been performed.
(2)	Telomeres are sections of non-coding DNA at the ends of chromosomes that protect coding DNA from deterioration during cell replication and other cellular processes [40,41]. Cell replication damages telomeres and studies suggest that the loss of telomere length over time causes the progression of ageing and shortening of lifespan [42]. However, oestrogen stimulates a promoter of the telomerase enzyme [43], which heals damaged telomeres by adding telomeric base pairs to its ends and indirectly activates other DNA repairing pathways [40]. Although we do not know whether oestrogen is important in all of our study species, it is possible that the effect of oestrogen on telomerase activation could help to explain the smaller decrease in lifespan when females are the heterogametic sex.
(3)	In many cases, males experience more intense sexual competition than females, as they are more reproductively efficient and so take more risks when pursuing a mating opportunity (e.g. males fighting for access to females or to establish their territory) [44,45]. Usually, females are not as efficient at reproducing, contribute more to their offspring than fathers, and so are predicted to engage in lower-risk behaviours [44–46]. Higher mortality in males owing to side effects of sexual selection, in combination with the effect of sex chromosomes on longevity, could also explain why there is a smaller lifespan difference between ZW females and ZZ males in comparison with XY males and XX females [11,15,44].

Understanding the mechanisms underpinning the substantial difference in lifespan dimorphism in male versus female heterogametic species is an important direction for future research, as this may improve our understanding of the factors that affect ageing. There is a multibillion-dollar industry in extending human lifespan [47], however, there is a crucial knowledge gap and we have much to learn about the basic biology underpinning longevity and the drivers of lifespan differences across sexes and species. Here, we have provided the first evidence that the heterogametic sex does, on average, die earlier than its homogametic counterpart across a range of taxa. We also found that lifespan dimorphism between the sexes is greater in male heterogametic species in comparison with female heterogametic species. These findings are a crucial step in uncovering the underlying mechanisms affecting longevity, which could point to pathways for extending life. We can only hope that more answers are found in our lifetime.