Abstract
Epidemiological studies of human longevity found two interesting features, robust advantage of female lifespan and consistent reduction of lifespan variation. To help understand the genetic aspects of these phenomena, the current study examined sex differences and variation of longevity using previously published mouse data sets including data on lifespan, age of puberty, and circulating insulin‐like growth factor 1 (IGF1) levels in 31 inbred strains, data from colonies of nuclear‐receptor‐interacting protein 1 (Nrip1) knockout mice, and a congenic strain, B6.C3H‐Igf1. Looking at the overall data for all inbred strains, the results show no significant difference in lifespan and lifespan variation between sexes; however, considerable differences were found among and within strains. Across strains, lifespan variations of female and male mice are significantly correlated. Strikingly, between sexes, IGF1 levels correlate with the lifespan variation and maximum lifespan in different directions. Female mice with low IGF1 levels have higher variation and extended maximum lifespan. The opposite is detected in males. Compared to domesticated inbred strains, wild‐derived inbred strains have elevated lifespan variation due to increased early deaths in both sexes and extended maximum lifespan in female mice. Intriguingly, the sex differences in survival curves of inbred strains negatively associated with age of female puberty, which is significantly accelerated in domesticated inbred strains compared to wild‐derived strains. In conclusion, this study suggests that genetic factors are involved in the regulation of sexual disparities in lifespan and lifespan variation, and dissecting the mouse genome may provide novel insight into the underlying genetic mechanisms.
Highlights
Epidemiological studies of human lifespan data revealed that the sex difference in human longevity is one of the most robust features of human populations
It is interesting that our results show the opposite directions of the association between insulin-like growth factor 1 (IGF1) with maximum lifespan between sexes (Figure S3), and the sexual differences are significant at all three time points (6, 12, and 18 months, Table S4)
As with the association between IGF1 and variation of lifespan, IGF1 levels at six months negatively associated with the median of absolute difference (MAD) of age of vaginal patency (AVP) (R = 0.37, p = 0.046, Figure 4a)
Summary
Epidemiological studies of human lifespan data revealed that the sex difference in human longevity is one of the most robust features of human populations (reviewed in Austad & Fischer, 2016). Unlike in the human, common used laboratory models, worms, fruit flies, rats and mice, show there is no robust difference in longevity between sexes (Austad & Fischer, 2016) Another important feature of human lifespan data identified by epidemiological studies is the inverse association between increased lifespan expectancy and decreased lifespan variation, which refers to the variation of age at death (Austad & Fischer, 2016; Raalte et al, 2018). The impact of anti-aging interventions on the lifespan variation of mice, defined as the median of absolute difference (MAD) between individual lifespan and the median lifespan of a population, is treatment-dependent and sexually dimorphic (Bartke et al, 2019) These results indicate that biological mechanisms might be involved in regulating variability of lifespan. These data provided us with a unique opportunity to investigate the genetic regulation of lifespan variation—including conditions that generate sex differences in lifespan and lifespan variation—across a wide variety of well-studied genotypes
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