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Age (Dordr). 2013 Feb;35(1):11-22. doi: 10.1007/s11357-011-9324-3. Epub 2011 Nov 12.

MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9.

Author information

1
Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.

Abstract

Evidence for a regulatory role of the miR-34 family in senescence is growing. However, the exact role of miR-34 in aging in vivo remains unclear. Here, we report that a mir-34 loss-of-function mutation in Caenorhabditis elegans markedly delays the age-related physiological decline, extends lifespan, and increases resistance to heat and oxidative stress. We also found that RNAi against autophagy-related genes, atg4, bec-1, or atg9, significantly reversed the lifespan-extending effect of the mir-34 mutants. Furthermore, miR-34a inhibits Atg9A expression at the post-transcriptional level in vitro, and the miR-34a binding sequences in the 3'-UTR of Atg9A contributes to the modulation of Atg9A expression by miR-34a. Our results demonstrate that the C. elegans mir-34 mutation extends lifespan by enhancing autophagic flux in C. elegans, and that miR-34 represses autophagy by directly inhibiting the expression of the autophagy-related proteins Atg9 in mammalian cells.

PMID:
22081425
PMCID:
PMC3543738
DOI:
10.1007/s11357-011-9324-3
[Indexed for MEDLINE]
Free PMC Article

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