BACKGROUND: Skin photoaging, clinically characterized by wrinkles and hyperpigmentation, accounts for 80% of extrinsic aging. Chronic UV exposure drives this process via oxidative damage. However, its synergistic axis with mitochondrial dysfunction remains mechanistically elusive. This study aims to elucidate the mechanistic link between mitochondrial oxidative stress and UV-induced photoaging, focusing on reactive oxygen species overproduction as a central driver of cellular decline.
METHODS: Through integrative analysis of molecular pathways and experimental validation, we investigated mitochondrial dysfunction, ROS accumulation, and UV-induced damage in skin cells. Therapeutic interventions, including mitochondrial-targeted antioxidants (e.g., MitoQ) and protective agents, were tested to assess their efficacy in restoring mitochondrial integrity and mitigating oxidative stress.
RESULTS: UV radiation exacerbates mitochondrial dysfunction by inducing ROS overproduction, mtDNA mutations and membrane permeability alterations, creating a vicious cycle that accelerates skin aging. Conversely, mitochondrial oxidative stress amplifies UV-induced damage, promoting collagen degradation and apoptosis. Interventions targeting mitochondrial function, such as MitoQ and mesenchymal stem cell-derived exosomes, significantly reduced ROS levels, preserved membrane potential, and enhanced skin resilience. Notably, PINK1/Parkin-mediated mitophagy and STAT3/p53 pathways were identified as critical regulators of mitochondrial homeostasis during photoaging.
CONCLUSION: This study clarifies the bidirectional relationship between mitochondrial stress and photoaging, highlighting ROS as a pivotal mediator. Restoring mitochondrial function via antioxidants or mitophagy enhancers offers actionable strategies to delay skin aging. These findings provide a foundation for novel anti-aging therapies with potential clinical and cosmetic applications.
