Journal
NATURE REVIEWS MOLECULAR CELL BIOLOGY
Volume 19, Issue 9, Pages 579-593Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41580-018-0033-y
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Funding
- National Institute on Aging [R01AG038664, R01AG037514, R01AG049157, R01AG040288]
- National Institute of General Medical Sciences [R01GM117466]
- Ellison Medical Foundation
- American Federation for Aging Research
- UK Dementia Research Institute (Medical Research Council)
- UK Dementia Research Institute (Alzheimer Disease Research UK)
- UK Dementia Research Institute (Alzheimer Disease Society)
- Wellcome Trust [095317/Z/11/Z]
- Rosetrees Trust
- Cambridge Institute for Medical Research [100140/Z/12/Z]
- Alzheimer Disease Research UK
- Tau Consortium
- Biomedical Research Centre at Addenbrooke's Hospital
- MRC [UKDRI-2002] Funding Source: UKRI
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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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