Overexpression of Atg5 in mice activates autophagy and extends lifespan

Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK · 2013 · Nature Communications · Atlas ID PYO2013

What this study shows

Mice engineered with extra copies of the autophagy gene Atg5 lived 17% longer and were leaner and more insulin-sensitive.

Abstract

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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.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (Atg5-overexpressing transgenic)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (Atg5-overexpressing transgenic)
Journal	Nature Communications
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ncomms3300 · PMID 23939249 · Free full text (PMC3753544)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Genetic (Atg5 overexpression)
Target	Autophagy (Atg5)
Model	Mouse (Atg5-overexpressing transgenic)
Effect	Ubiquitous Atg5 overexpression enhances autophagy and extends median mouse lifespan by ~17%
Dose	Atg5 cDNA inserted into pCAGGS vector driven by cytomegalovirus enhancer and chicken β-actin promoter, expressed ubiquitously in transgenic mice.
Sample size	n=65 for WT mice and n=70 for Atg5 Tg mice (line 25, combined sex); n=25 for WT and n=30 for other Atg5 Tg lines (43, 47, 471).
Effect size	Median lifespan of Atg5 Tg mice (line 25) was 119 days (~17%) longer than WT (P <0.001); maximum lifespan was 900±34 days for Atg5 Tg vs 781±22 days for WT (P <0.01).
Limitations	not stated

In the Atlas

Open questions that cite this study

Cited as supporting evidence for the open question How much of rapamycin's healthspan benefit runs through fewer senescent cells?.
Cited as supporting evidence for the open question Is autophagy actually REQUIRED for the mammalian lifespan benefit?.

Answers that reference this study

Discussed in the plain-language answer Is autophagy actually required for the lifespan benefit of mTOR inhibition?.

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Want to understand the biology behind this study? → mTOR and Autophagy

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