Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.
Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.
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DOI：
10.1111/acel.13891
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发表时间：
2023-08
期刊：
影响因子：
7.8
通讯作者：
Nelson, James F.
中科院分区：
文献类型：
--
作者：
Jiang, Nisi;Cheng, Catherine J.;Gelfond, Jonathan;Strong, Randy;Diaz, Vivian;Nelson, James F.
人们已经广泛观察到衰老和寿命的性别差异，在整个人类群体中，女性一直比男性长寿。然而，对造成这些差异的机制仍然知之甚少。在这项研究中，我们通过青春期前去势遗传异质性（UM‐HET3）小鼠（一种模拟人类年龄相关死亡率性别差异的独特小鼠模型）探索了青春期后睾丸效应对衰老性别差异的影响。青春期前阉割通过降低男性早期至中年死亡率并延长其中位寿命以与女性相匹配，消除了性别之间的寿命差异。此外，去势延长了体重增长的持续时间，减弱了雄性动物早期体重与寿命之间的负相关性，使其生长轨迹与雌性动物一致。我们的研究结果表明，遗传多样性小鼠的青春期后睾丸活动是寿命和生长轨迹性别差异的主要原因。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和开发潜在的长寿干预措施提供了基础。男性的寿命比女性短，从成年早期开始死亡率较高，但没有已知的确切机制。在这里，我们发现青春期前去势消除了遗传异质性小鼠模型中寿命和生长的性别差异，这表明睾丸的存在在这些性别差异中起着致病作用。
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. Males live shorter than females and experience higher mortality rates since early adulthood with no known definitive mechanisms. Here we found prepubertal castration eliminated sex differences in longevity and growth in a genetically heterogeneous mouse model, which indicates the presence of testes plays a causative role in these sex differences.
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