User:Joe Betts-LaCroix/The Hallmarks of Aging



"The Hallmarks of Aging" is a seminal peer-reviewed article published in the journal Cell in June 2013 by the European researchers Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer.

The paper's name is a reference to the 2000 paper The Hallmarks of Cancer, which, as of 2011, was Cell's most cited paper at over 15,000 citations, and which had a fundamental impact on the field of cancer research. True to its namesake, *The Hallmarks of Aging* has, according to Google Scholar as of 2020, been cited over 6,000 times. https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=%22the+hallmarks+of+aging%22&btnG= It has made a fundamental contribution to the field of aging research and spawned numerous spinoffs and derivatives.

As a testament to the significance of this paper, the title has come to signify not just the paper, but more generically the various causes of aging itself https://www.afar.org/what-are-the-hallmarks-of-aging

The tremendous impact of the article is due to the authors laying out, for the first time in the aging field, a rational rubric for including each underlying mechanism of the aging process in their list. They did so by defining criteria for an ideal hallmark: "(1) it should manifest during normal aging; (2) its experimental aggravation should accelerate aging; and (3) its experimental amelioration should retard the normal aging process and hence increase healthy lifespan."

By applying these criteria, the authors proposed nine hallmarks of aging:
 * genomic instability,
 * telomere attrition,
 * epigenetic alterations,
 * loss of proteostasis,
 * deregulated nutrient sensing,
 * mitochondrial dysfunction,
 * cellular senescence,
 * stem cell exhaustion, and
 * altered intercellular communication.

They grouped these hallmarks into three categories:
 * primary hallmarks (causes of damage): genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis
 * antagonistic hallmarks (responses to damage): deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence
 * integrative hallmarks (culprits of the phenotype): stem cell exhaustion, altered intercellular communication