Oxidative Stress in Stem Cell Aging

Abstract

Stem cell aging is a process in which stem cells progressively lose their ability to self-renew or differentiate, succumb to senescence or apoptosis, and eventually become functionally depleted. Unresolved oxidative stress and concomitant oxidative damages of cellular macromolecules including nucleic acids, proteins, lipids, and carbohydrates have been recognized to contribute to stem cell aging. Excessive production of reactive oxygen species and insufficient cellular antioxidant reserves compromise cell repair and metabolic homeostasis, which serves as a mechanistic switch for a variety of aging-related pathways. Understanding the molecular trigger, regulation, and outcomes of those signaling networks is critical for developing novel therapies for aging-related diseases by targeting stem cell aging. Here we explore the key features of stem cell aging biology, with an emphasis on the roles of oxidative stress in the aging process at the molecular level. As a concept of cytoprotection of stem cells in transplantation, we also discuss how systematic enhancement of endogenous antioxidant capacity before or during graft into tissues can potentially raise the efficacy of clinical therapy. Finally, future directions for elucidating the control of oxidative stress and developing preventive/curative strategies against stem cell aging are discussed.

Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

“…However, telomere shortening over time limits the number of cell divisions. [29,31] Therefore, telomere attrition corresponds with the cell replicative lifespan. [30] A ribonucleoprotein reverse transcriptase called telomerase can delay either cell fate by elongating telomeres.…”

Impaired Regulation of Redox Transcriptome during the Differentiation of iPSCs into Induced Cardiomyocytes (iCMs)

“…Under normal/unstressed conditions, RCS play a key role in cellular physiological signaling and regulate normal cellular processes such as induction of proliferation, cell-cycle, and differentiation (23, 24). However, an excessive accumulation of RCS induces oxidative stress leading to apoptotic, necrotic and fibrotic events (25, 26). In fact, RCS signaling is necessary for the differentiation of iPS into iCM (23, 27), but a chronic increase in RCS is detrimental to these cells as it could impair both the proliferation and differentiation processes (24, 25).…”

“…However, an excessive accumulation of RCS induces oxidative stress leading to apoptotic, necrotic and fibrotic events (25, 26). In fact, RCS signaling is necessary for the differentiation of iPS into iCM (23, 27), but a chronic increase in RCS is detrimental to these cells as it could impair both the proliferation and differentiation processes (24, 25). Real time quenching of RCS is vital to maintain redox homeostasis, which is often controlled through multiple biochemical events.…”

Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis

“…Reactive oxygen and nitrogen species (ROS/RNS) are by-products of normal aerobic metabolism and are involved in the complex regulation of several signaling pathways including cell proliferation, survival, and inflammation [1][2][3][4][5][6][7][8][9]. Imbalance between ROS/RNS and antioxidant function results in oxidative/ nitrosative stress that contributes to pathology in a range of clinical contexts including ageing and multiple sclerosis (MS) [10][11][12][13].…”