与Sirtuin相关的人类衰老程序汇聚在胎盘特定基因PAPPA的激活上
Shijia Bi1, Xiaoyu Jiang2, Qianzhao Ji2
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Developmental cell
|March 14, 2024
概括
赛尔图因缺乏会通过改变基因组组织和激活PAPPA基因来加速细胞衰老. 这一发现为衰老干预措施和潜在的衰老生物标志物提供了新的见解.
科学领域:
- 遗传学和表观遗传学
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 赛尔图因因其在长寿和染色质调节中的作用而闻名.
- 西尔图因功能与它们对细胞衰老的影响之间的确切联系尚不清楚.
研究的目的:
- 为了研究Sirtuins (SIRT1-SIRT7) 在细胞衰老中的作用.
- 阐明Sirtuin缺乏如何影响基因组组织和基因表达.
- 为了确定衰老干预的潜在治疗目标.
主要方法:
- 产生具有SIRT1-SIRT7淘汰的同质人体干细胞系.
- 大规模的表观基因组分析,以评估基因组组织.
- 进行3D染色体架构调查,绘制增强剂-促进剂相互作用的地图.
主要成果:
- 人类干细胞中的Sirtuin缺乏导致细胞衰老加速.
- 赛尔图因缺乏会改变基因组组织,特别是在活性增强剂,促进新的增强剂-促进剂循环.
- 在Sirtuin缺乏细胞中,PAPPA基因的异常激活驱动了亲衰老效应,并表明PAPPA是衰老的生物标志物.
结论:
- 赛尔图因对于维持基因组稳定性和防止细胞过早衰老至关重要.
- 这项研究揭示了一种链接Sirtuin功能,3D基因组组织和衰老的机制.
- 这些发现为开发针对Sirtuin通路和PAPPA激活的新型衰老干预措施提供了基础.
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