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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2021; 13(11): 1714-1732
Published online Nov 26, 2021. doi: 10.4252/wjsc.v13.i11.1714
Why stem/progenitor cells lose their regenerative potential
Angela Picerno, Alessandra Stasi, Rossana Franzin, Claudia Curci, Ighli di Bari, Loreto Gesualdo, Fabio Sallustio
Angela Picerno, Alessandra Stasi, Rossana Franzin, Claudia Curci, Ighli di Bari, Loreto Gesualdo, Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari 70124, Italy
Fabio Sallustio, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Bari 70124, Italy
Author contributions: Picerno A, Stasi A, Franzin R, Curci C, di Bari I, Gesualdo L and Sallustio F collected the data and contributed to the writing of the manuscript; Sallustio F and Picerno A devised the project, developed the main conceptual ideas and edited the manuscript; all authors revised and approved the final version.
Conflict-of-interest statement: None of the authors have any conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fabio Sallustio, PhD, Assistant Professor, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare, 11, Bari 70124, Italy. fabio.sallustio@uniba.it
Received: March 26, 2021
Peer-review started: March 26, 2021
First decision: May 12, 2021
Revised: May 26, 2021
Accepted: October 31, 2021
Article in press: October 31, 2021
Published online: November 26, 2021
Processing time: 243 Days and 18 Hours
Abstract

Nowadays, it is clear that adult stem cells, also called as tissue stem cells, play a central role to repair and maintain the tissue in which they reside by their self-renewal ability and capacity of differentiating into distinct and specialized cells. As stem cells age, their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired. From a molecular perspective, these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration (i.e epigenomic profile) as well as changes in the tissue microenviroment, both into the niche and by systemic circulating factors. Strikingly, it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Therefore, understanding how resident stem cell age and affects near and distant tissues is fundamental. Here, we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number, function and phenotype that determine the loss of tissue renewal properties. Furthermore, we examine the possible cell rejuvenation strategies. Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.

Keywords: Stem cells; Aging; Self-renewal; Rejuvenation; Aging-associated disorders; Epigenetic changes; Aging environment

Core Tip: Aging influences the ability of stem cell renewal, inducing a gradual functional decline of adult tissue-specific stem cells in maintaining homeostasis of the tissue and playing a role in the pathophysiology of various aging-associated disorders. Stem cell rejuvenation strategies may reverse this aging phenotype.