Skin Aging and Mitochondrial Dysfunction: Structural Changes, Mechanistic Insights, and Therapeutic Perspectives

Area of Science:

• Dermatology and Gerontology
• Mitochondrial Biology
• Cellular Aging

Background:

• Skin aging is characterized by structural and functional decline.
• Mitochondrial dysfunction is increasingly recognized as a key contributor to this process.
• Oxidative stress, originating from mitochondrial metabolism, plays a central role in cellular senescence.

Purpose of the Study:

• To review the relationship between skin structural changes and mitochondrial function during aging.
• To evaluate emerging therapeutic interventions for mitochondrial dysfunction in skin aging.
• To synthesize current evidence on the role of mitochondria in cutaneous aging and senescence.

Main Methods:

• A narrative review of 49 scientific articles published between 2015 and 2025.
• Literature search using keywords such as 'skin aging,' 'mitochondrial dysfunction,' 'oxidative stress,' and 'cutaneous senescence' in databases like PubMed, Scopus, and ScienceDirect.
• Inclusion of original research articles based on thematic relevance, recency, and scientific rigor, with additional searches for therapeutic interventions.

Main Results:

• Oxidative stress from mitochondrial metabolism is a primary driver of skin cell senescence.
• Mitochondrial dysfunction links oxidative stress, inflammation (inflammaging), and the senescence-associated secretory phenotype (SASP) to skin aging.
• Age-related decline in mitochondrial DNA copy number and increased reactive oxygen species production impair skin homeostasis and energy metabolism.

Conclusions:

• Mitochondrial dysfunction is a critical pathogenic mechanism in skin aging, driven by oxidative stress.
• Emerging mitochondrial-targeted therapies (e.g., NAD+ precursors, CoQ10, senolytics) show potential for anti-aging benefits.
• Further clinical validation, standardized biomarkers, and long-term safety data are crucial for implementing these therapies.