老年男性的正常精子发生与代偿性转录组变化有关
Normal spermatogenesis in older men is associated with compensatory transcriptome changes.
摘要(中文译文)
男性生殖衰老是一个复杂过程，涉及睾丸及其他部位进行性的、有害的组织学和生理学改变。年龄相关疾病常会干扰生殖功能，使得难以区分全身性衰老与男性生殖衰老。我们此前已表明，健康衰老与完整的精子发生、正常的精子生成和激素分泌相关。然而，使人类睾丸能够在无明显功能丧失的情况下衰老的分子机制仍不明确。在本研究中，我们通过对来自年轻（24-31岁，n=4）、中年（41-45岁，n=3）和老年（54-75岁，n=6）男性的具有完整精子发生的睾丸样本进行批量RNA测序，研究了衰老人类睾丸的转录组动力学。我们发现，在健康人类睾丸中，衰老与广泛的可变剪接事件相关，影响涉及代谢通路和DNA修复的基因。此外，我们识别出衰老过程中显著的转录变化，尤其与炎症和氧化应激相关。重要的是，一部分呈现年龄依赖性表达模式的基因参与双链断裂（DSBs）的形成和DNA修复，并在减数分裂早期表达。在一个独立验证队列中，对DSBs标志物γH2AX的定量未显示生殖系中与年龄相关的DSBs异常积累。这些发现提供了对人类睾丸健康衰老过程中所发生转录变化的全面认识，我们假设这些变化反映了有助于在人类男性中随时间推移保持生殖能力的代偿机制。
Abstract
Male reproductive ageing is a complex process involving progressive and detrimental histological and physiological alterations to the testis and beyond. Age-related morbidities often confound reproductive function, making it difficult to disentangle systemic from reproductive male ageing. We have previously shown that healthy ageing is associated with full spermatogenesis, normal sperm production and hormonal secretion. However, the molecular mechanisms allowing the human testis to age without major loss of function remained elusive. In this study, we investigated the transcriptomic dynamics of the ageing human testis using bulk RNA sequencing of testicular samples with full spermatogenesis from young (24-31 years, n = 4), middle-aged (41-45 years, n = 3), and aged (54-75 years, n = 6) men. We found that, in healthy human testis, ageing is associated with widespread alternative splicing events, affecting genes involved metabolic pathways and DNA repair. Moreover, we identified significant transcriptional changes during ageing, particularly associated with inflammation and oxidative stress. Importantly, a subset of genes showing age-dependent expression patterns was involved in the formation of double-strand breaks (DSBs) and DNA repair and was expressed during early meiosis. Quantification of γH2AX, a marker of DSBs, in an independent validation cohort, did not show age-related abnormal accumulation of DSBs in the germline. These findings provide a comprehensive view of the transcriptional changes occurring during healthy ageing in the human testis, and we hypothesise that these reflect compensatory mechanisms that help preserve reproductive capacity over time in human males.
如何引用
AMA
Yihan Wang, Sven Berres, Henrike Krenz, Tobias Tekath, Marius Wöste, Sarah Sandmann, et al. Normal spermatogenesis in older men is associated with compensatory transcriptome changes.. GeroScience. 2026; doi:10.1007/s11357-026-02403-8.
APA
Yihan Wang, Sven Berres, Henrike Krenz, Tobias Tekath, Marius Wöste, Sarah Sandmann, et al (2026). Normal spermatogenesis in older men is associated with compensatory transcriptome changes.. GeroScience. https://doi.org/10.1007/s11357-026-02403-8
GB/T 7714
Yihan Wang, Sven Berres, Henrike Krenz, Tobias Tekath, Marius Wöste, Sarah Sandmann, et al. Normal spermatogenesis in older men is associated with compensatory transcriptome changes.[J]. GeroScience, 2026 doi:10.1007/s11357-026-02403-8.
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