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Priority Research Paper|Volume 12, Issue 5|pp 4052—4066

Survey of senescent cell markers with age in human tissues

M. Laura Idda1,2, Waverly G. McClusky1, Valeria Lodde1,3, Rachel Munk1, Kotb Abdelmohsen1, Martina Rossi1, Myriam Gorospe1
  • 1Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
  • 2Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Sassari, Italy
  • 3Department of Biomedical Sciences, University of Sassari, Sassari, Italy
Received: January 11, 2020Accepted: February 20, 2020Published: March 11, 2020

Copyright © 2020 Idda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Cellular senescence, triggered by sublethal damage, is characterized by indefinite growth arrest, altered gene expression patterns, and a senescence-associated secretory phenotype. While the accumulation of senescent cells during aging decreases tissue function and promotes many age-related diseases, at present there is no universal marker to detect senescent cells in tissues. Cyclin-dependent kinase inhibitors 2A (p16/CDKN2A) and 1A (p21/CDKN1A) can identify senescent cells, but few studies have examined the numbers of cells expressing these markers in different organs as a function of age. Here, we investigated systematically p16- and p21-positive cells in tissue arrays designed to include normal organs from persons across a broad spectrum of ages. Increased numbers of p21-positive and p16-positive cells with donor age were found in skin (epidermis), pancreas, and kidney, while p16-expressing cells increased in brain cortex, liver, spleen and intestine (colon), and p21-expressing cells increased in skin (dermis). The numbers of cells expressing p16 or p21 in lung did not change with age, and muscle did not appear to have p21- or p16-positive cells. In summary, different organs display different levels of the senescent proteins p16 and p21 as a function of age across the human life span.