The Sam and Ann Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, Texas, USA.
Department of Cellular and Integrative Physiology, UT Health San Antonio, San Antonio, Texas, USA.
Aging Cell. 2023 Aug;22(8):e13891. doi: 10.1111/acel.13891. Epub 2023 May 23.
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.
衰老和长寿过程中的性别差异已被广泛观察到，在人类群体中，女性的寿命始终长于男性。然而，驱动这些差异的机制仍知之甚少。在这项研究中，我们通过对遗传异质性（UM-HET3）小鼠进行青春期前阉割来探究青春期后睾丸效应对衰老过程中性别差异的影响，这是一种独特的小鼠模型，可模拟人类与年龄相关的死亡率方面的性别差异。青春期前阉割消除了性别间的长寿差异，降低了雄性中观察到的早期至中年死亡率升高的水平，并延长了其中位寿命，使其与雌性相匹配。此外，阉割延长了体重增长的持续时间，并减弱了雄性中早期体重与寿命之间的反比关系，使它们的生长轨迹与雌性的生长轨迹一致。我们的研究结果表明，遗传多样化小鼠青春期后的睾丸作用主要负责寿命以及生长轨迹方面的性别差异。这些发现为进一步研究驱动性别特异性衰老模式的基本机制以及开发潜在的延长寿命干预措施奠定了基础。
