Abstract
Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health.
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Acknowledgements
E.F.F. was supported by HELSE SØR-ØST (2017056, 2020001 and 2021021), the Research Council of Norway (262175 and 277813), the National Natural Science Foundation of China (81971327), Akershus University Hospital (269901 and 261973), the Civitan Norges Forskningsfond for Alzheimers sykdom (for a three-year PhD fellowship, 281931), the Czech Republic–Norway KAPPA programme (with M. Vyhnálek, TO01000215) and the Rosa sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society (207819). J.L. is supported by a BBSRC David Phillips Fellowship (BB/P005535/1), a BBSRC Responsive Mode Grant (BB/T013273/1), an AMS Springboard Award (SBF004\1051) and a Wellcome Trust ISSF award (ISSF3/H17RCO/NG18). A.K.S. is supported by Wellcome Trust Investigator Award 103830/Z/14/Z. A.S. is supported by the Norwegian Cancer Society (171318) and the Research Council of Norway (221831) and its Centres of Excellence funding scheme (262652), as well as by HELSE SØR-ØST (2020032). T.J. is supported by the Norwegian Cancer Society (190214) and the Research Council of Norway (249884). N.T. was supported by grants from the European Research Council (ERC GA695190, MANNA; ERC-GA737599, NeuronAgeScreen). M.H. is supported by the National Institutes of Health (AG038664 and GM117466) as well as by the American Federation for Aging Research and the Larry L. Hillblom Foundation. R.M. is supported by the National Institutes of Health (AG057296 and AG054407), the Tau Consortium and the Daniel F. and Ada L. Rice Foundation. D.C.R. is supported by the UK Dementia Research Institute (funded by the MRC), Alzheimer’s Research UK and the Alzheimer’s Society (UKDRI-2002 to D.C.R.), the Tau Consortium, Alzheimer’s Research UK, an anonymous donation to the Cambridge Centre for Parkinson-Plus and the Roger de Spoelberch Prize. I.B. is supported by funding from the European Research Council (ERC PoC 842174) and the Cancer Research UK City of London Centre Award (C7893/A28990). L.P. is supported by a Wellcome Trust Collaborative Award, the Max Planck Society and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement number 268739. G.K. is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Ruban Rose”; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); the Leducq Foundation; the RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001. All figures were created with BioRender.com.
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E.F.F. has a CRADA arrangement with ChromaDex and is a consultant to Aladdin Healthcare Technologies, the Vancouver Dementia Prevention Centre and Intellectual Labs. A.K.S. is a consultant to Oxford Healthspan. D.C.R. is a consultant for Aladdin Healthcare Technologies, Drishti Discoveries and Nido Biosciences. G.K. is a scientific co-founder of everImmune, Samsara Therapeutics and Therafast Bio. All other authors declare no competing interests.
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Aman, Y., Schmauck-Medina, T., Hansen, M. et al. Autophagy in healthy aging and disease. Nat Aging 1, 634–650 (2021). https://doi.org/10.1038/s43587-021-00098-4
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DOI: https://doi.org/10.1038/s43587-021-00098-4
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