Abstract
Significance: Mesenchymal stem cells (MSCs), adult stem cells with the potential of differentiation into mesodermal lineages, play an important role in tissue homeostasis and regeneration. In different organs, a subpopulation of MSCs is located near the vasculature and possibly represents the original source of lineage-committed mesenchymal progenitors.Recent Advances: The plasticity and immune characteristics of MSCs render them a preferential tool for regenerative cell therapy.Critical Issues: The culture expansion needed before MSC transplantation is associated with cellular senescence. Moreover, accelerated senescence of the total and perivascular MSC pool has been observed in humans and mouse models of premature aging disorders. MSC dysfunction is acknowledged as a culprit for the aging-associated degeneration of mesodermal tissues, but the underlying epigenetic pathways remain elusive. This article reviews current understanding of mechanisms impinging on MSC health, including oxidative stress, Nrf2-antioxidant responsive element activity, sirtuins, noncoding RNAs, and PKCs.Future Directions: We provide evidence that epigenetic profiling of MSCs is utilitarian to the prediction of therapeutic outcomes. In addition, strategies that target oxidative stress-associated mechanisms represent promising approaches to counteract the detrimental effect of age and senescence in MSCs.—Antioxid. Redox Signal. 29, 864–879.
Highlights
Understanding the aging process and the mechanisms underpinning the development of aging-associated diseases represents one of the most important endeavors of modern medical research
A similar effect was described for miR-503, a miR that we found to be dysregulated in diabetes, a pathological condition associated with aging and senescence of endothelial cells (ECs), which is transferred from ECs to pericytes inducing dysfunction [10, 12]
Among the emerged long noncoding RNA (lncRNA) associated with senescence, one that has been investigated in Mesenchymal stem cells (MSCs) with functional consequences is HOTAIR, an lncRNA associated with a chromatin locus that is important for epigenetic changes and that is altered in cardiac disease of aging [37, 89]
Summary
Understanding the aging process and the mechanisms underpinning the development of aging-associated diseases represents one of the most important endeavors of modern medical research. Strategies that target oxidative stress-associated mechanisms represent promising approaches to counteract the detrimental effect of age and senescence in MSCs.—Antioxid. This article reviews current understanding of the contribution of oxidative stress as a trigger of modifications at DNA and RNA leading to MSC aging and senescence (Fig. 1).
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