Multi-layered Regulatory Mechanisms and Translational Implications of Mitochondrial Redox Imbalance in Aging Stem Cells.
Abstract
Mitochondrial redox homeostasis is required for proper stem cell fate determination and tissue regeneration, and its dysregulation is a hallmark of aging-related stem cell dysfunction. This review systematically summarizes the multi-layered mechanisms by which aging-induced mitochondrial redox imbalance impairs stem cell identity, covering reactive oxygen species homeostasis, macromolecular metabolism, mitochondrial DNA integrity, mitochondrial dynamics, and the Sirtuin/forkhead box O (FoxO) signaling axis. We further highlight the context-specific metabolic features across different stem cell types and recent advances in targeted interventions to restore mitochondrial redox homeostasis, with a special focus on small molecule compounds with translational potential. This review further critically evaluates conflicting experimental evidence in current research, highlights major unresolved controversies and technical limitations in the field, providing a model that links mitochondrial redox status to epigenetic regulation for advancing both basic research and translational applications of mitochondrial redox-targeted interventions for stem cell aging.
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Research summary
This review proposes that restoring mitochondrial redox homeostasis can reverse stem cell dysfunction and aging by linking metabolic status to epigenetic regulation. The paper is relevant as it addresses fundamental hallmarks of aging (mitochondrial dysfunction and stem cell exhaustion) rather than just treating symptoms, but as a review summarizing existing mechanisms and controversies, its direct scientific impact is limited to synthesis rather than novel experimental breakthroughs.
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