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PMID: 16373574 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

A developmental timing microRNA and its target regulate life span in C. elegans.

Science (New York, N.Y.) ·Vol. 310 ·No. 5756 ·2005-12-23 ·Pages 1954-7

Boehm M, Slack F

Abstract

The microRNA lin-4 and its target, the putative transcription factor lin-14, control the timing of larval development in Caenorhabditis elegans. Here, we report that lin-4 and lin-14 also regulate life span in the adult. Reducing the activity of lin-4 shortened life span and accelerated tissue aging, whereas overexpressing lin-4 or reducing the activity of lin-14 extended life span. Lifespan extension conferred by a reduction in lin-14 was dependent on the DAF-16 and HSF-1 transcription factors, suggesting that the lin-4-lin-14 pair affects life span through the insulin/insulin-like growth factor-1 pathway. This work reveals a role for microRNAs and developmental timing genes in life-span regulation.

MeSH Terms
Aging/genetics,physiology Amino Acid Sequence Animals Caenorhabditis elegans/genetics,physiology Caenorhabditis elegans Proteins/genetics,metabolism,physiology Forkhead Transcription Factors Gene Expression Regulation, Developmental Genes, Developmental Heat-Shock Response Insulin/metabolism Insulin-Like Growth Factor I/metabolism Lipofuscin/metabolism Longevity/genetics,physiology MicroRNAs/physiology Molecular Sequence Data Mutation Nuclear Proteins/genetics,physiology RNA, Helminth/physiology Receptor, Insulin/metabolism Repressor Proteins/physiology Signal Transduction Transcription Factors/physiology
Chemicals
Caenorhabditis elegans Proteins Forkhead Transcription Factors Insulin LIN-14 protein, C elegans Lipofuscin MicroRNAs Nuclear Proteins RNA, Helminth Repressor Proteins Transcription Factors daf-16 protein, C elegans lin-4 microRNA, C elegans Insulin-Like Growth Factor I DAF-2 protein, C elegans Receptor, Insulin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Boehm Michelle
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
Slack Frank
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2005-12-23
Pages
1954-7
Language
English
Region
United States
NLM ID
0404511
Subset
IM
Grants
NIGMS NIH HHS · R01 GM064701 · United States
NIGMS NIH HHS · GM64701 · United States
Corrections
CommentIn
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