The aging of the global population is linked to an increase in age-related diseases. The kidneys undergo both structural and functional declines with age, and aging is a significant risk factor for kidney diseases. Mitochondrial dysfunction is recognized as a crucial factor affecting kidney aging. Although the importance of disrupted mitochondrial homeostasis in renal aging has gained increasing attention, the associations and causal mechanisms have not been systematically summarized.
Recent Advances:
Mitochondria are highly dynamic organelles that operate in various functions, including cell metabolism, redox regulation, cell division, and cell death, and are closely associated with both cell senescence and kidney diseases. Furthermore, aging is also associated with mitochondrial redox dysfunction, abnormal calcium homeostasis, impaired quality control (QC), and increased mitochondrial DNA (mtDNA) leakages. Mitochondrial dysfunction and cellular senescence may sustain a vicious cycle in renal injury. Several types of drugs show promising potential in alleviating renal injury by modulating mitochondria-related aging phenotypes.
Critical Issues:
Dysregulated redox status, mitochondrial metabolic reprogramming, mtDNA abnormalities, impaired mitochondrial QC, and mitochondrial calcium overload are the factors that establish a self-perpetuating vicious cycle that promotes renal aging. In addition, the roles of mitochondria-associated senescence in both acute kidney injury and chronic kidney disease are examined and summarized, with potential differences and promising interventions targeting mitochondrial dysfunction and cell senescence also highlighted.
Future Directions:
Clinically available interventions specifically aimed at addressing mitochondrial aging remain underdeveloped and require further clinical trials. Future research should also focus on creating drugs that can precisely target mitochondrial senescence to prevent the progression of age-related kidney diseases. Antioxid. Redox Signal. 44, 464–487.
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