MicroRNAs both promote and antagonize longevity in C. elegans.
MicroRNAs both promote and antagonize longevity in C. elegans.
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DOI：
10.1016/j.cub.2010.11.015
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发表时间：
2010-12-21
期刊：
影响因子：
9.2
通讯作者：
Slack, Frank J.
中科院分区：
文献类型：
--
作者：
de Lencastre, Alexandre;Pincus, Zachary;Zhou, Katherine;Kato, Masaomi;Lee, Siu Sylvia;Slack, Frank J.
线虫的衰老是由基因控制的，但调节寿命的机制并不完全清楚。MicroRNAs(MiRNAs)调节发育和新陈代谢的各个方面，其中一种miRNA以前被认为与寿命有关。在这里，我们证明了多个miRNAs在线虫衰老中改变了表达，包括新的miRNAs，并且几个最上调的miRNAs的突变导致寿命缺陷。有些起到了延长正常寿命和抵抗压力的作用，而有些则抑制了这些现象。我们发现这些miRNAs在基因上与DNA损伤检查点反应通路和胰岛素信号通路中的基因相互作用。我们的发现表明，miRNAs对寿命有积极和消极的影响。由于几个在衰老过程中上调的miRNAs在保守的衰老途径中调节基因，从而影响线虫的寿命，我们认为miRNAs可能在更复杂的生物体的应激反应和衰老中发挥重要作用。
Aging is under genetic control in C. elegans but the mechanisms of lifespan regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism and one miRNA has been previously implicated in lifespan. Here we show that multiple miRNAs change expression in C. elegans aging, including novel miRNAs, and that mutations in several of the most up-regulated miRNAs lead to lifespan defects. Some act to promote normal lifespan and stress resistance while others inhibit these phenomena. We find that these miRNAs genetically interact with genes in the DNA damage checkpoint response pathway and in the insulin signaling pathway. Our findings reveal that miRNAs both positively and negatively influence lifespan. Since several miRNAs up-regulated during aging regulate genes in conserved pathways of aging and thereby influence lifespan in C. elegans, we propose that miRNAs may play important roles in stress response and aging of more complex organisms.
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