人类淋巴细胞中的复制应激反应在衰老过程中发生性别特异性变化
Melanie Rall-Scharpf1, Dominik Schlotter1, Philipp Koch2
1Department of Obstetrics and Gynecology, Ulm University, 89075 Ulm, Germany.
Nucleic acids research
|June 18, 2025
概括
衰老对男性和女性的DNA修复有不同的影响. 男性的DNA修复基因活性增加,而女性的Fanconi贫血路径功能减少,揭示了性别特定的衰老策略.
科学领域:
- 基因组学就是基因组学.
- 衰老研究研究 衰老研究
- 细胞生物学 细胞生物学
背景情况:
- 衰老与疾病发病率的增加和预期寿命的性别差距有关,这表明性别特异性的衰老过程.
- 基因组不稳定性是衰老的一个关键因素,但性别特异性差异仍然不明.
研究的目的:
- 调查DNA损伤反应 (DDR) 和衰老过程中的复制应激的性别特异性.
- 为了确定基因组不稳定性背后的分子机制在老年男性和女性.
主要方法:
- 分析来自不同年龄的男性和女性捐献者的外周血液淋巴细胞 (PBL) 和造血干细胞和原始细胞 (HSPC) 中的DNA损伤反应 (DDR).
- 转录组分析以确定DDR通路中的性别依赖的表达变化.
- 功能性测定包括复制动力学,PCNA无化,转化合成 (TLS) - 聚合酶活性,以及对TLS-聚合酶抑制剂的敏感性.
主要成果:
- 转录组学揭示了DDR路径中与年龄相关的显著性别依赖的变化. 男人显示了DNA修复和复制叉重塑组件的调节.
- 年龄较大的女性在Fanconi贫血路径中表现出较低的活性,这表明对复制应激转化合成 (TLS) 的转变.
- 老年男性的PBL显示出高度依赖PARP活动,尽管复制动态没有改变,复制压力减少.
结论:
- 在老年人中,出现了不同的性别特定的应对复制压力的策略.
- 女性可能使用DNA损伤耐受路径切换,而男性则依赖PARP激活.
- 这些性别特异性机制有助于与年龄相关的基因组稳定性下降.
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