Pan-tissue transcriptome analysis reveals sex-dimorphic human aging.

IF 6.4 1区生物学 Q1 BIOLOGY

eLife Pub Date : 2025-10-03 DOI:10.7554/eLife.102449

Siqi Wang, Danyue Dong, Xin Li, Zefeng Wang

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Abstract

Complex diseases often exhibit sex dimorphism in morbidity and prognosis, many of which are age-related. However, the underlying mechanisms of sex-dimorphic aging remain foggy, with limited studies across multiple tissues. We systematically analyzed ~17,000 transcriptomes from 35 human tissues to quantitatively evaluate the individual and combined contributions of sex and age to transcriptomic variations. We discovered extensive sex dimorphisms during aging with distinct patterns of change in gene expression and alternative splicing (AS). Intriguingly, the male-biased age-associated AS events have a stronger association with Alzheimer's disease, and the female-biased events are often regulated by several sex-biased splicing factors that may be controlled by estrogen receptors. Breakpoint analysis showed that sex-dimorphic aging rates are significantly associated with decline of sex hormones, with males having a larger and earlier transcriptome change. Collectively, this study uncovered an essential role of sex during aging at the molecular and multi-tissue levels, providing insight into sex-dimorphic regulatory patterns.

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泛组织转录组分析揭示性别二态人类衰老。

复杂疾病在发病率和预后方面往往表现出性别二态性，其中许多与年龄有关。然而，性别二态衰老的潜在机制仍然不清楚，跨多种组织的研究有限。我们系统地分析了来自35个人体组织的约17,000个转录组，以定量评估个体和性别和年龄对转录组变异的综合贡献。我们在衰老过程中发现了广泛的性别二态性，在基因表达和选择性剪接（AS）方面具有不同的变化模式。有趣的是，男性偏倚的年龄相关的AS事件与阿尔茨海默病有更强的相关性，而女性偏倚的事件通常受几种可能由雌激素受体控制的性别偏倚剪接因子的调节。断点分析表明，性别二态老化率与性激素的下降显著相关，雄性的转录组变化更大、更早。总的来说，这项研究在分子和多组织水平上揭示了性别在衰老过程中的重要作用，为性别二态调节模式提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

eLife BIOLOGY-

CiteScore

12.90

自引率

3.90%

发文量

3122

审稿时长

17 weeks

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