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

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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.

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Acknowledgments

We thank Dr. Mengqiu Dong (National Institute of Biological Science, Beijing,China) for providing helpful discussions and materials, Dr. Nektarios Tavernarakis (Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Crete, Greece) for providing the pL4440-bec-1 plasmids, and Dr. Christian Mϋnz (Institute of Experimental Immunology, Department of Pathology, University Hospital of Zurich, Zurich, Switzerland) for the donation of the pEGFP-HLC3 plasmids.

This work was supported by a grant (2007CB507400) from the National Basic Research Program of China to XMC.

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Authors and Affiliations

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

    Jurong Yang & Yani He

  2. Department of Nephrology, Chinese PLA Nephrology of Institute & Key Lab, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, People’s Republic of China

    Jurong Yang, Dapeng Chen, Zhe Feng, Quan Hong, Xueyuan Bai, Qinggang Li, Guangyan Cai, Jianzhong Wang & Xiangmei Chen

  3. Medical College, NanKai University, Tianjin, People’s Republic of China

    Dapeng Chen

  4. Department of Biology, Queens College, 65-30 Kissena Boulevard, Flushing, New York, USA

    Alicia Meléndez

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  1. Jurong Yang
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Correspondence to Xiangmei Chen.

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Jurong Yang and Dapeng Chen contributed equally to this work.

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Yang, J., Chen, D., He, Y. et al. MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9. AGE 35, 11–22 (2013). https://doi.org/10.1007/s11357-011-9324-3

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  • DOI: https://doi.org/10.1007/s11357-011-9324-3

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