title: MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9.
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.
authors.affiliation: Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Jurong
authors.initials: J
authors.lastname: Yang
authors.forename: Dapeng
authors.initials: D
authors.lastname: Chen
authors.forename: Yani
authors.initials: Y
authors.lastname: He
authors.forename: Alicia
authors.initials: A
authors.lastname: Meléndez
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Li
authors.forename: Guangyan
authors.initials: G
authors.lastname: Cai
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wang
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D000071183:Autophagy-Related Proteins; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017238:Genes, Helminth; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics*; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033921:Vesicular Transport Proteins
chemical_list: C000594371:ATG9A protein, rat; C549015:Atg9A protein, mouse; D000071183:Autophagy-Related Proteins; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins
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