Overexpression of Atg5 in mice activates autophagy and extends lifespan

Jong Ok Pyo; Seung Min Yoo; Hye Hyun Ahn; Jihoon Nah; Se Hoon Hong; Tae In Kam; Sunmin Jung; Yong Keun Jung

doi:10.1038/ncomms3300

Overexpression of Atg5 in mice activates autophagy and extends lifespan

Jong Ok Pyo, Seung Min Yoo, Hye Hyun Ahn, Jihoon Nah, Se Hoon Hong, Tae In Kam, Sunmin Jung, Yong Keun Jung

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347 Scopus citations

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.

Original language	English (US)
Article number	2300
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3300
State	Published - 2013
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms3300

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@article{0a2d822142c94f6491d9b5d5ce616900,

title = "Overexpression of Atg5 in mice activates autophagy and extends lifespan",

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.",

author = "Pyo, {Jong Ok} and Yoo, {Seung Min} and Ahn, {Hye Hyun} and Jihoon Nah and Hong, {Se Hoon} and Kam, {Tae In} and Sunmin Jung and Jung, {Yong Keun}",

note = "Funding Information: We thank Dr N. Mizushima (Tokyo Medical and Dental University, Japan) for providing GFP-LC3 Tg mice and K.H. Pyo (Seoul National University Hospital) for the assistance of data analysis. Dr J.-O.P. and Mr S.-M.Y. were supported by BK21 program. This work was supported by the grants from the Global Research Laboratory (GRL, K21004000002-12A0500-00210), Creative Research Initiative (CRI)-Acceleration Research (2013R1A2A1A01016896) and the Ubiquitome project (20120006127) funded by the Ministry of Education, Science and Technology (MEST) in Korea.",

year = "2013",

doi = "10.1038/ncomms3300",

language = "English (US)",

volume = "4",

journal = "Nature communications",

issn = "2041-1723",

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T1 - Overexpression of Atg5 in mice activates autophagy and extends lifespan

AU - Pyo, Jong Ok

AU - Yoo, Seung Min

AU - Ahn, Hye Hyun

AU - Nah, Jihoon

AU - Hong, Se Hoon

AU - Kam, Tae In

AU - Jung, Sunmin

AU - Jung, Yong Keun

N1 - Funding Information: We thank Dr N. Mizushima (Tokyo Medical and Dental University, Japan) for providing GFP-LC3 Tg mice and K.H. Pyo (Seoul National University Hospital) for the assistance of data analysis. Dr J.-O.P. and Mr S.-M.Y. were supported by BK21 program. This work was supported by the grants from the Global Research Laboratory (GRL, K21004000002-12A0500-00210), Creative Research Initiative (CRI)-Acceleration Research (2013R1A2A1A01016896) and the Ubiquitome project (20120006127) funded by the Ministry of Education, Science and Technology (MEST) in Korea.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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Overexpression of Atg5 in mice activates autophagy and extends lifespan

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ASJC Scopus subject areas

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