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Review
. 2023 Jan 19;186(2):243-278.
doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3.

Hallmarks of aging: An expanding universe

Carlos López-Otín  1 , Maria A Blasco  2 , Linda Partridge  3 , Manuel Serrano  4 , Guido Kroemer  5
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Free article
Review

Hallmarks of aging: An expanding universe

Carlos López-Otín et al. Cell. .
Free article

Abstract

Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organizational features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.

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Conflict of interest statement

Declaration of interests M.A.B. is founder and shareholder of Life Length, SL, which commercializes telomere length measurements for biomedical use. M.S. is shareholder and advisor of Rejuveron Senescence Therapeutics, AG, and Altos Labs, Inc.; and shareholder of Senolytic Therapeutics, Inc., and Life Biosciences, Inc. G.K. has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sotio, Tollys, Vascage, and Vasculox/Tioma; consulting for Reithera and is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics, and Therafast Bio. G.K. is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis, and metabolic disorders and has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys, and Vascage; has been consulting for Reithera; is on the Board of Directors of the Bristol Myers Squibb Foundation France, and is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics, and Therafast Bio. G.K.’s wife, Laurence Zitvogel has held research contracts with 9 Meters Biopharma, Daiichi Sankyo, Pilege, was on the on the Board of Directors of Transgene, is a co-founder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. G.K.’s brother, Romano Kroemer, was an employee of Sanofi and has consulted for Boehringer-Ingelheim. None of the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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