4.7 Article

Autophagy and the hallmarks of aging

Journal

AGEING RESEARCH REVIEWS
Volume 72, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.arr.2021.101468

Keywords

Aging; Chaperones; Lysosomes; Organelle turnover; Proteostasis; Proteolysis

Funding

  1. National Institutes of Health (USA) [AG054108, AG021904, AG017617, AG038072, AG031782, NS100717, DK098408, P30AG038072, P30DK041296, DK124308]
  2. Fondo de Investigacion Sanitaria-Instituto de Salud Carlos III (Spain)-FEDER [PI20/00728]
  3. Spanish Ministry of Science and Innovation (Spain) [RTI2018-097948-A-100, RYC-2016-20480]
  4. JPB Foundation (USA)
  5. Rainwater Charitable Foundation (USA)
  6. Glenn Foundation (USA)
  7. Backus Foundation (USA)
  8. Robert and Renee Belfer (USA)
  9. Grace Science Foundation (USA)
  10. Michael J Fox Foundation (USA)
  11. Silverstein Foundation (USA)
  12. BBVA Foundation (Spain)

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Autophagy, as an essential cellular process, plays a crucial role in cellular quality control and proteostasis. Dysfunction of autophagy with age contributes significantly to the loss of proteostasis in aging organisms. The diverse functions of different types of autophagy and their interactions with other aging determinants place autophagy at the center of the aging process.
Autophagy, an essential cellular process that mediates degradation of proteins and organelles in lysosomes, has been tightly linked to cellular quality control for its role as part of the proteostasis network. The current interest in identifying the cellular and molecular determinants of aging, has highlighted the important contribution of malfunctioning of autophagy with age to the loss of proteostasis that characterizes all old organisms. However, the diversity of cellular functions of the different types of autophagy and the often reciprocal interactions of autophagy with other determinants of aging, is placing autophagy at the center of the aging process. In this work, we summarize evidence for the contribution of autophagy to health-and lifespan and provide examples of the bidirectional interplay between autophagic pathways and several of the so-called hallmarks of aging. This central role of autophagy in aging, and the dependence on autophagy of many geroprotective interventions, has motivated a search for direct modulators of autophagy that could be used to slow aging and extend healthspan. Here, we review some of those ongoing therapeutic efforts and comment on the potential of targeting autophagy in aging.

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