Overexpression of Atg5 in mice activates autophagy and extends lifespan

By Jong-Ok Pyo, Seung-Min Yoo, Hye-Hyun Ahn, Jihoon Nah, Se-hoon Hong, T. Kam, Sunmin Jung, Yong-Keun Jung. Nature Communications, 2013

680 citations recorded by the source corpus.

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. Changes in autophagy have been shown to modulate lifespan in lower organisms. Here, Pyo et al.show that mice globally overexpressing the autophagy protein Atg5 live longer and are leaner than normal mice, providing the first evidence that increased autophagy extends lifespan in mammals.

Subfields: Aging, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/dea035b0b932bfd922689c937cb33b23eb42ca3f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. Guido Kroemer
2. D. Rubinsztein

In Epidemiology

1. Guido Kroemer
2. L. Galluzzi
3. D. Rubinsztein
4. Fiona M Menzies
5. Frank Madeo
6. Angeleen Fleming
7. C. López‐Otín
8. Beth Levine

In Molecular Biology

1. Guido Kroemer
2. L. Galluzzi
3. D. Rubinsztein
4. Fiona M Menzies
5. Frank Madeo
6. C. López‐Otín
7. Beth Levine
8. Douglas R. Green

Citations in the corpus

• Metabolic Control of Longevity. (2016, background): “Genetic manipulations designed to promote autophagy, such as systemic overexpression of the essential component of the autophagic machinery Atg5, increase longevity and improve insulin sensitivity, leanness, and motor function in mice (Pyo et al., 2013).”
• Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities. (2017, positive): “Overexpression of ATG5 in mice induces autophagy and extends lifespan, and is associated with anti-ageing phenotypes including leanness, increased insulin sensitivity and improved motor function (Pyo et al., 2013).”