单细胞分析确定了独立的衰老过程,这些过程在芽酵母菌中竞争决定细胞命运
Manuel Hotz1, Rachel G Kroll-Ling1, Nathaniel H Thayer1
1Calico Life Sciences LLC, South San Francisco, CA 94080.
概括
老化的酵母细胞表现出多种分子变化,包括核糖体DNA (rDNA) 的不稳定性和线粒体衰退. 这些过程可以同时发生,挑战以前的假设,并建议对衰老的"竞争性危害模型".
科学领域:
- 细胞生物学 细胞生物学
- 衰老的研究研究.
- 酵母遗传学 酵母遗传学
背景情况:
- 现型异质性在衰老中很常见,但其分子基础尚不清楚.
- 酵母的不同衰老轨迹,包括核糖体DNA (rDNA) 不稳定或线粒体衰退,被认为是相互排斥的.
研究的目的:
- 研究老化的酵母细胞中异质性的分子驱动因素.
- 为了澄清rDNA不稳定性,线粒体功能和衰老过程中的压力反应之间的关系.
主要方法:
- 单细胞转录组学 单细胞转录组学
- 纵向光显微镜 纵向光显微镜
- 有针对性的基因干扰.
主要成果:
- 在老化的酵母中确定了不同的转录反应,包括rDNA沉默的丧失,缺氧反应和环境应激反应 (ESR).
- ESR是线粒体衰退的结果,而不是rDNA的不稳定性,是生物标志物,而不是寿命决定因素.
- rDNA的不稳定性和线粒体功能障碍可以同时发生,这与相互排他性相矛盾.
结论:
- 提出了一个"竞争性危险模型",其中独立的衰老过程并行进行.
- 衰老轨迹是由第一个达到关键失效的过程决定的.
- 解开了衰老途径之间的因果关系,并为理解衰老异质性提供了一个框架.
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