MicroRNAs both promote and antagonize longevity in C. elegans.
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 life 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.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511 USA.
Alexandre
A
de Lencastre
Zachary
Z
Pincus
Katherine
K
Zhou
Masaomi
M
Kato
Siu Sylvia
SS
Lee
Frank J
FJ
Slack
D000375:Aging / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological
D035683:MicroRNAs; D007334:Insulin-Like Growth Factor I