期刊:Nature
发表时间:2023/04/12
数字识别码:10.1038/s41586-023-05922-y
摘要:Physiological homeostasis becomes compromised during ageing, as a result of impairment of cellular processes, including transcription and RNA splicing1,2,3,4. However, the molecular mechanisms leading to the loss of transcriptional fidelity are so far elusive, as are ways of preventing it. Here we profiled and analysed genome-wide, ageing-related changes in transcriptional processes across different organisms: nematodes, fruitflies, mice, rats and humans. The average transcriptional elongation speed (RNA polymerase II speed) increased with age in all five species. Along with these changes in elongation speed, we observed changes in splicing, including a reduction of unspliced transcripts and the formation of more circular RNAs. Two lifespan-extending interventions, dietary restriction and lowered insulin–IGF signalling, both reversed most of these ageing-related changes. Genetic variants in RNA polymerase II that reduced its speed in worms5 and flies6 increased their lifespan. Similarly, reducing the speed of RNA polymerase II by overexpressing histone components, to counter age-associated changes in nucleosome positioning, also extended lifespan in flies and the division potential of human cells. Our findings uncover fundamental molecular mechanisms underlying animal ageing and lifespan-extending interventions, and point to possible preventive measures.
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摘要翻译(由计算机程序完成,仅供参考,内容以英文原文为准):
衰老过程中,由于包括转录和RNA剪接在内的细胞过程受损,生理稳态受到损害1,2,3,4。然而,导致转录保真度丧失的分子机制以及预防转录保真度的方法迄今尚不明确。在这里,我们描述并分析了不同生物体(线虫、果蝇、小鼠、大鼠和人类)转录过程中与衰老相关的全基因组变化。在所有五个物种中,平均转录延伸速度(RNA聚合酶II速度)随着年龄的增长而增加。随着延伸速度的变化,我们观察到剪接的变化,包括未剪接转录物的减少和更多环状RNA的形成。两种延长寿命的干预措施,即饮食限制和降低胰岛素-胰岛素样生长因子信号传导,都逆转了大多数与衰老相关的变化。RNA聚合酶II的遗传变异降低了其在蠕虫中的速度。秀丽隐杆线虫ama-1和ama-2基因的致死和鹅膏素抗性突变。遗传学120409–422(1988)。“>5并飞行6延长了它们的寿命。同样,通过过表达组蛋白成分来降低RNA聚合酶II的速度,以对抗与年龄相关的核小体定位变化,也延长了苍蝇的寿命和人类细胞的分裂潜力。我们的发现揭示了动物衰老和延长寿命干预的基本分子机制,并指出切实可行的预防措施</p>
所属学科:
基因组学
生理学
药明康德内容团队
每个人有朝一日都难免衰老,但随着生物技术的不断发展,科学家们正在开发各种全新的技术,来延缓衰老进程,甚至是逆转衰老。今日,由来自德国科隆大学(University of Cologne)的科学家们领衔、发布于国际顶尖科学期刊《自然》上的一项研究发现,五种不同动物(人类、果蝇、大鼠、小鼠和蠕虫)细胞的衰老过程似乎相类似,这项发现有助解释驱动衰老的因素,并为开发逆转衰老疗法打开一扇新的大门。
[1] Debès, C., Papadakis, A., Grönke, S. et al. Ageing-associated changes in transcriptional elongation influence longevity. Nature (2023). https://doi.org/10.1038/s41586-023-05922-y