TY - JOUR
T1 - MicroRNAs both promote and antagonize longevity in C. elegans
AU - De Lencastre, Alexandre
AU - Pincus, Zachary
AU - Zhou, Katherine
AU - Kato, Masaomi
AU - Lee, Siu Sylvia
AU - Slack, Frank J.
N1 - Funding Information:
We thank the Caenorhabditis Genetic Center for supplying strains. A.d.L. was supported by a National Research Service Award Postdoctoral Fellowship from the National Institutes of Health (NIH; 1F32AG030851). Z.P. was supported by a Jane Coffin Childs Postdoctoral Fellowship. F.J.S. was supported by a Breakthroughs in Gerontology grant from the American Federation for Aging Research, the Ellison Medical Foundation, and the NIH (AG033921).
PY - 2010/12/21
Y1 - 2010/12/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650490230&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2010.11.015
DO - 10.1016/j.cub.2010.11.015
M3 - Article
C2 - 21129974
AN - SCOPUS:78650490230
SN - 0960-9822
VL - 20
SP - 2159
EP - 2168
JO - Current Biology
JF - Current Biology
IS - 24
ER -