Mitochondrial health and metabolic remodeling: Translational strategies for successful aging and healthspan extension

Mitochondrial dysfunction drives systemic metabolic remodeling during aging, shifting tissues toward maladaptive energetic states that promote chronic inflammation, cellular senescence, and organ decline. Beyond their role as energy producers, mitochondria act as signaling hubs that integrate nutrient availability, redox status, and epigenetic cues to coordinate tissue homeostasis. As these regulatory functions erode with age, the resulting mitochondrial stress propagates across organ systems, manifesting as metabolic disease, immunosenescence, and reduced regenerative capacity. Critically, mitochondria are increasingly recognised as tractable therapeutic targets: a growing toolkit of pharmacological, genetic, and lifestyle interventions has demonstrated the potential to restore mitochondrial resilience and slow or reverse aspects of the aging phenotype.This Research Topic focuses on the translational and systemic dimensions of mitochondrial aging, from how mitochondrial decline reshapes whole-body metabolism and tissue function, to the development and validation of interventions that promote mitochondrial health, successful aging, and healthspan extension. We particularly welcome studies that bridge the gap between experimental models and human aging, including clinical trials, longitudinal cohort analyses, and biomarker development. Research addressing tissue-specific responses to mitochondrial stress and resilience, including skeletal muscle, brain, heart, and liver, is strongly encouraged.We invite submissions addressing, but not limited to, the following topics:- Systemic consequences of mitochondrial aging: How mitochondrial decline drives metabolic remodeling, inflammation, immunosenescence, and reduced organ resilience at the whole-body level.- Mitochondria–senescence axis: The role of mitochondrial stress in triggering and sustaining the senescence-associated secretory phenotype (SASP) and its systemic consequences.- Nutrient sensing and epigenetic regulation: How pathways such as mTOR, AMPK, sirtuins, and NAD+ metabolism link mitochondrial status to epigenetic control of aging.- Pharmacological and nutraceutical interventions: NAD+ precursors, senolytics, mitochondria-targeted antioxidants, and other compounds that restore mitochondrial function in aged tissues.- Lifestyle and physiological interventions: Exercise, caloric restriction, fasting regimens, and their effects on mitochondrial biogenesis and metabolic flexibility across the lifespan.- Mitochondrial transplantation and gene therapy: Emerging cell and gene-based strategies to replace or repair dysfunctional mitochondria in aged or diseased tissues.- Clinical biomarkers of mitochondrial resilience: Development and validation of blood-, tissue-, or imaging-based biomarkers to quantify mitochondrial health in human aging and interventional studies. Topic editors: Naibo Feng, Zhongwen Qi, Modi Yang Source: https://www.frontiersin.org/research-topics/83081/mitochondrial-health-and-metabolic-remodeling-translational-strategies-for-successful-aging-and-healthspan-extension