Study: Epidermal Mitochondrial Loss Linked to Skin Aging and Fat Gain

A new study published in the Journal of Investigative Dermatology suggests mitochondrial decline in epidermal keratinocytes plays a central role in skin aging and may also contribute to age-related obesity.

Researchers at Kumamoto University examined both aged wild-type mice models and mice models engineered to lack mitochondrial transcription factor A (TFAM) in epidermal cells. 

According to the results, keratinocytes from aged mice showed significantly reduced mitochondrial DNA content and diminished mitochondrial respiratory capacity. Mice with targeted TFAM deletion in keratinocytes (Tfam^EKO) recapitulated these aging-associated phenotypes by middle age, despite normal expression of senescence markers. Tfam^EKO mice also showed impaired hair regrowth and slower wound healing.

Tfam^EKO mice also developed obesity over time, accumulating more subcutaneous fat and showing elevated fasting glucose levels despite comparable food intake and energy expenditure to controls. The authors said this suggested  impaired mitochondrial fatty acid metabolism in keratinocytes may have systemic metabolic consequences, potentially contributing to obesity in aging populations.

“Age-related loss of mitochondria in epidermal cells occurs independently of cellular senescence and contributes to age-related hair thinning and delayed wound healing and possibly obesity," the authors concluded. "Our findings demonstrate a potential link between skin aging and age-related weight gain due to decline of mitochondrial function in skin cells.”

Source: Yamamura S, et al. Journal of Investigative Dermatology. 2025;145(10):2464-2473. doi:10.1016/j.jid.2025.03.028