Aging-associated mitochondrial decline accelerates skin aging and obesity

Skin tissue, which consists of epidermal, dermal, and hypodermal cells, plays an important role in biological defense and physical appearance. External and internal stresses occurring with aging disrupt skin homeostasis, promoting development of phenotypes associated with aging. While many studies of skin aging focus on the dermis, potential epidermal changes have largely remained uncharacterized. Here, we demonstrate that epidermal cells do not exhibit cellular senescence phenotypes with aging but instead show age-related decreases in mitochondrial number. We also found that mice lacking mitochondrial transcription factor A (TFAM) in epidermal cells exhibit delayed hair regrowth and impaired wound healing by middle age resembling changes seen in skin of aged mice. Furthermore, middle-aged epidermis-specific TFAM-deficient mice exhibited obesity, suggesting that impaired fatty acid metabolism in epidermal cells resulting from mitochondrial decline may lead to obesity. These findings overall suggest that mitochondrial decline occurs as a primary event in epidermal aging, and that anti-aging strategies to enhance activity or number of epidermal mitochondria could antagonize both skin-aging phenotypes and age-related metabolic disease.