第二军医大学刘智勇团队的研究发现综合单核转录组学和染色质可及性分析揭示了人类睾丸衰老的关键分子基础。这一研究成果于2026年3月9日发表在国际顶尖学术期刊《分子细胞生物学报》上。

为了阐明人类睾丸衰老的机制，该研究团队对来自年轻人和老年人的病理证实的非肿瘤睾丸组织的单核转录组和染色质可及性（snRNA-seq和snATAC-seq）进行了综合分析。他们的综合多组学分析揭示了睾丸转录组中显著的年龄诱导改变，特别是影响与精子发生相关的基因。在支持细胞和间质细胞中也观察到明显的年龄相关变化，随着年龄的增长，支持细胞对环境影响的敏感性增加。

此外，Wnt转运体Wntless （WLS）的表达在老年睾丸支持细胞中大幅上调，这与细胞衰老和紧密连接的破坏有关。在体外，支持细胞中过表达WLS可显著加速衰老，这表明WLS可能在睾丸衰老中起潜在作用。他们的研究提供了人类睾丸在衰老过程中转录组和染色质可及性变化的详细多组学图谱，为这些变化背后的细胞和分子机制提供了见解，并确定了针对男性生殖健康年龄相关下降的干预的潜在治疗靶点。

据了解，人类睾丸是男性生殖的重要器官，主要负责精子发生和雄激素的产生。随着男性年龄的增长，睾丸功能下降，但其潜在的分子机制仍未得到很好的理解。

附：英文原文

Title: Integrated single-nucleus transcriptomic and chromatin accessibility analysis reveals key molecular basis of human testicular aging

Author: Sun, Weihao, Liu, Hongyu, Pang, Pengcheng, Ren, Guanyu, Feng, Zhuanghui, Wang, Lei, Piao, Shuguang, He, Miaoxia, Shen, Haoyu, Li, Jinsong, Li, Xin, Yang, Chenghua, Wang, Linhui, Liu, Zhiyong

Issue&Volume: 2026-03-09

Abstract: The human testis, a crucial organ in male reproduction, is mainly responsible for spermatogenesis and androgen production. As men age, testicular function declines, yet the underlying molecular mechanisms are still not well understood. To elucidate the mechanisms of human testicular aging, we performed an integrated analysis of single-nucleus transcriptomes and chromatin accessibility (snRNA-seq and snATAC-seq) on pathologically confirmed non-tumor testicular tissues from young and aged individuals. Our integrated multi-omic analysis reveals significant age-induced alterations in the testis transcriptome, particularly affecting genes linked to spermatogenesis. Significant age-related changes were also observed in Sertoli and Leydig cells, with Sertoli cells exhibiting increased sensitivity to environmental influences as age. Furthermore, the expression of Wntless (WLS), a Wnt transporter, was substantially upregulated in Sertoli cells of aged testes, which was correlated with cellular senescence and the disruption of tight junctions. Overexpression of WLS in Sertoli cells significantly accelerated senescence in vitro, implying a potential role for WLS in testicular aging. Our study provides a detailed multi-omic map of the transcriptomic and chromatin accessibility changes in the human testis during aging, offering insights into the cellular and molecular mechanisms behind these changes, and identifying potential therapeutic targets for interventions against age-related declines in male reproductive health.

DOI: 10.1093/jmcb/mjag001

Source: https://dx.doi.org/10.1093/jmcb/mjag001