MicroRNAs Both Promote and Antagonize Longevity in C-elegans

被引：220

作者：

de Lencastre, Alexandre ^{[1
]}

Pincus, Zachary ^{[1
]}

Zhou, Katherine ^{[1
]}

Kato, Masaomi ^{[1
]}

Lee, Siu Sylvia ^{[2
]}

Slack, Frank J. ^{[1
]}

机构：

[1] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA

[2] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14850 USA

来源：

CURRENT BIOLOGY | 2010年 / 20卷 / 24期

基金：

美国国家卫生研究院;

关键词：

LIFE-SPAN; CAENORHABDITIS-ELEGANS; GENES; RNAS; EXPRESSION; 21U-RNAS; GENETICS; LONG;

D O I：

10.1016/j.cub.2010.11.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Aging is under genetic control in C. elegans, but the mechanisms of life-span regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism, and one miRNA has been previously implicated in life span. Results: Here we show that multiple miRNAs change expression in C. elegans aging, including novel miRNAs, and that mutations in several of the most upregulated miRNAs lead to life-span defects. Some act to promote normal life span and stress resistance, whereas 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. Conclusions: Our findings reveal that miRNAs both positively and negatively influence lite span. Because several miRNAs upregulated during aging regulate genes in conserved pathways of aging and thereby influence life span in C. elegans, we propose that miRNAs may play important roles in stress response and aging of more complex organisms.

引用

页码：2159 / 2168

页数：10

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