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Overexpression of Atg5 in mice activates autophagy and extends lifespan

Author

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  • Jong-Ok Pyo

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Seung-Min Yoo

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Hye-Hyun Ahn

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Jihoon Nah

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Se-Hoon Hong

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Tae-In Kam

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Sunmin Jung

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

  • Yong-Keun Jung

    (Global Research Laboratory, School of Biological Sciences/Bio-MAX Institute, Seoul National University)

Abstract

Autophagy has been implicated in the ageing process, but whether autophagy activation extends lifespan in mammals is unknown. Here we show that ubiquitous overexpression of Atg5, a protein essential for autophagosome formation, extends median lifespan of mice by 17.2%. We demonstrate that moderate overexpression of Atg5 in mice enhances autophagy, and that Atg5 transgenic mice showed anti-ageing phenotypes, including leanness, increased insulin sensitivity and improved motor function. Furthermore, mouse embryonic fibroblasts cultured from Atg5 transgenic mice are more tolerant to oxidative damage and cell death induced by oxidative stress, and this tolerance was reversible by treatment with an autophagy inhibitor. Our observations suggest that the leanness and lifespan extension in Atg5 transgenic mice may be the result of increased autophagic activity.

Suggested Citation

  • Jong-Ok Pyo & Seung-Min Yoo & Hye-Hyun Ahn & Jihoon Nah & Se-Hoon Hong & Tae-In Kam & Sunmin Jung & Yong-Keun Jung, 2013. "Overexpression of Atg5 in mice activates autophagy and extends lifespan," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3300
    DOI: 10.1038/ncomms3300
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    Cited by:

    1. Cristal M. Hill & Diana C. Albarado & Lucia G. Coco & Redin A. Spann & Md Shahjalal Khan & Emily Qualls-Creekmore & David H. Burk & Susan J. Burke & J. Jason Collier & Sangho Yu & David H. McDougal & , 2022. "FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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