This narrative review discusses the relationship between structural changes in the skin and mitochondrial function during aging and evaluates emerging therapeutic interventions targeting mitochondrial dysfunction. An analysis of 49 scientific articles published between 2015 and 2025 was conducted using descriptors including “skin aging,” “mitochondrial dysfunction,” “oxidative stress,” and “cutaneous senescence,” and articles were retrieved from PubMed, Scopus, and ScienceDirect. Additional research was conducted using terms related to therapeutic interventions, including “mitochondrial therapies AND skin aging OR cutaneous aging.” Original research articles were included based on thematic relevance, recency, and scientific rigor. The reviewed studies suggest that oxidative stress, mainly from mitochondrial metabolism, is a primary cause of skin cell senescence. Mitochondrial dysfunction emerges as a central mechanistic hub linking oxidative stress, mitochondrial genome instability, chronic low‐grade inflammation (inflammaging), and the senescence‐associated secretory phenotype (SASP) to age‐related structural and functional skin alterations. Mitochondria maintain skin homeostasis through cell proliferation, differentiation, and genetic material synthesis. With advancing age, mitochondrial DNA copy number declines significantly, while reactive oxygen species production increases, thereby compromising cellular energy metabolism. Emerging mitochondrial‐targeted therapeutic strategies, including nicotinamide adenine dinucleotide (NAD + ) precursors, coenzyme Q10 supplementation, senolytics, and modulators of mitochondrial quality control, show promising effects on skin aging parameters in preclinical and early clinical studies. However, current evidence is based on small clinical trials with short follow‐up periods, and long‐term safety data remain limited. Therefore, while mitochondria are not the sole source of oxidants, growing evidence indicates that oxidative stress‐driven mitochondrial dysfunction represents a priority pathogenic mechanism in skin aging. The clinical translation of mitochondrial‐targeted therapies represents an innovative opportunity for anti‐aging strategies, although the validation of standardized biomarkers and longitudinal safety investigations remains critical for clinical implementation.
Bonotto et al. (Thu,) studied this question.