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Autophagy as a promoter of longevity: insights from model organisms.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Hansen, Malene 
Rubinsztein, David C  ORCID logo  https://orcid.org/0000-0001-5002-5263
Walker, David W 

Abstract

Autophagy is a conserved process that catabolizes intracellular components to maintain energy homeostasis and to protect cells against stress. Autophagy has crucial roles during development and disease, and evidence accumulated over the past decade indicates that autophagy also has a direct role in modulating ageing. In particular, elegant studies using yeasts, worms, flies and mice have demonstrated a broad requirement for autophagy-related genes in the lifespan extension observed in a number of conserved longevity paradigms. Moreover, several new and interesting concepts relevant to autophagy and its role in modulating longevity have emerged. First, select tissues may require or benefit from autophagy activation in longevity paradigms, as tissue-specific overexpression of single autophagy genes is sufficient to extend lifespan. Second, selective types of autophagy may be crucial for longevity by specifically targeting dysfunctional cellular components and preventing their accumulation. And third, autophagy can influence organismal health and ageing even non-cell autonomously, and thus, autophagy stimulation in select tissues can have beneficial, systemic effects on lifespan. Understanding these mechanisms will be important for the development of approaches to improve human healthspan that are based on the modulation of autophagy.

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Keywords

0601 Biochemistry and Cell Biology, Biomedical, Basic Science, Aging, Generic Health Relevance, 1.1 Normal biological development and functioning

Journal Title

Nat Rev Mol Cell Biol

Conference Name

Journal ISSN

1471-0072
1471-0080

Volume Title

19

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (095317/Z/11/Z)
Wellcome Trust (100140/Z/12/Z)