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Essential role for autophagy in life span extension
Frank Madeo, … , Maria Chiara Maiuri, Guido Kroemer
Frank Madeo, … , Maria Chiara Maiuri, Guido Kroemer
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):85-93. https://doi.org/10.1172/JCI73946.
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Review

Essential role for autophagy in life span extension

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Abstract

Life and health span can be prolonged by calorie limitation or by pharmacologic agents that mimic the effects of caloric restriction. Both starvation and the genetic inactivation of nutrient signaling converge on the induction of autophagy, a cytoplasmic recycling process that counteracts the age-associated accumulation of damaged organelles and proteins as it improves the metabolic fitness of cells. Here we review experimental findings indicating that inhibition of the major nutrient and growth-related signaling pathways as well as the upregulation of anti-aging pathways mediate life span extension via the induction of autophagy. Furthermore, we discuss mounting evidence suggesting that autophagy is not only necessary but, at least in some cases, also sufficient for increasing longevity.

Authors

Frank Madeo, Andreas Zimmermann, Maria Chiara Maiuri, Guido Kroemer

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Figure 1

Molecular mechanism of autophagosome formation and disposal of cellular material.

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Molecular mechanism of autophagosome formation and disposal of cellular ...
Pro-autophagic signals such as nutrient or growth factor depletion activate regulatory components of the autophagic machinery, such as the ULK1 and Beclin-1 complexes. Isolation membranes form at ER-mitochondrial interfaces or recycling endosomes under the guidance of the ATG machinery, which, among other components, consists of ATG7, ATG5-ATG12, and ATG16L. ATG7 drives the lipidation of LC3, which incorporates into the incipient phagophore to mediate the recognition and loading of cargo, such as protein aggregates, damaged organelles, or lipid droplets. The mature autophagosomes (not shown) fuse with lysosomes to form autolysosomes, through which the engulfed cellular material gets digested. As a result, potentially harmful misfolded protein aggregates or damaged organelles are detoxified, and their degradation products can be used to replenish cellular energy reserves and anabolic reactions.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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