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Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.

ABSTRACT: Sex differences in aging and longevity have been widely observed, with females consistently outliving males across human populations. However, the mechanisms driving these disparities remain poorly understood. In this study, we explored the influence of post-pubertal testicular effects on sex differences in aging by prepubertally castrating genetically heterogeneous (UM-HET3) mice, a unique mouse model that emulates human sex differences in age-related mortality. Prepubertal castration eliminated the longevity disparity between sexes by reducing the elevated early- to mid-life mortality rate observed in males and extending their median lifespan to match that of females. Additionally, castration extended the duration of body weight growth and attenuated the inverse correlation between early-age body weight and lifespan in males, aligning their growth trajectories with those of females. Our findings suggest that post-pubertal testicular actions in genetically diverse mice are primarily responsible for sex differences in longevity as well as growth trajectories. These findings offer a foundation for further investigation into the fundamental mechanisms driving sex-specific aging patterns and the development of potential pro-longevity interventions.

SUBMITTER: Jiang N

PROVIDER: S-EPMC10410013 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.

Jiang Nisi N Cheng Catherine J CJ Gelfond Jonathan J Strong Randy R Diaz Vivian V Nelson James F JF

Aging cell 20230523 8

Sex differences in aging and longevity have been widely observed, with females consistently outliving males across human populations. However, the mechanisms driving these disparities remain poorly understood. In this study, we explored the influence of post-pubertal testicular effects on sex differences in aging by prepubertally castrating genetically heterogeneous (UM-HET3) mice, a unique mouse model that emulates human sex differences in age-related mortality. Prepubertal castration eliminate ...[more]

PMID: 37221997

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Project description:ImportanceIf we assume that women and men exhibit variations of the same fundamental vascular physiology, then conventional analyses of subclinical measures would suggest that women catch up to men by midlife in the extent of potentially important vascular disease. Alternatively, under the assumption that vascular physiology may fundamentally differ between women and men, a sex-specific analysis of existing data could offer new insights and augment our understanding of sex differences in cardiovascular diseases.ObjectiveTo evaluate whether longitudinal patterns of blood pressure (BP) elevation differ between women and men during the life course when considering baseline BP levels as the reference.Design, setting, and participantsWe conducted sex-specific analyses of longitudinal BP measures (144 599 observations) collected for a period of 43 years (1971 to 2014) in 4 community-based US cohort studies. The combined total included 32 833 participants (54% female) spanning ages 5 to 98 years. Data were analyzed between May 4, 2019, and August 5, 2019.ExposuresAge and serially assessed longitudinal BP measures: systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure (PP).Main outcomes and measuresSex-specific change in each primary BP measure compared with baseline BP levels, derived from multilevel longitudinal models fitted over the age span, and new-onset cardiovascular disease events.ResultsOf the 32 833 participants, 17 733 were women (54%). Women compared with men exhibited a steeper increase in BP that began as early as in the third decade and continued through the life course (likelihood ratio test χ2 = 531 for systolic BP; χ2 = 123 for diastolic BP; χ2 = 325 for MAP; and χ2 = 572 for PP; P for all <.001). After adjustment for multiple cardiovascular disease risk factors, these between-sex differences in all BP trajectories persisted (likelihood ratio test χ2 = 314 for systolic BP; χ2 = 31 for diastolic BP; χ2 = 129 for MAP; and χ2 = 485 for PP; P for all <.001).Conclusions and relevanceIn contrast with the notion that important vascular disease processes in women lag behind men by 10 to 20 years, sex-specific analyses indicate that BP measures actually progress more rapidly in women than in men, beginning early in life. This early-onset sexual dimorphism may set the stage for later-life cardiovascular diseases that tend to present differently, not simply later, in women compared with men.

Dataset Information

Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.

Publications

Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.

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