Extracellular Superoxide Dismutase Prevents Skin Aging by Promoting Collagen Production through the Activation of AMPK and Nrf2/HO-1 Cascades

With aging, the skin becomes thin and drastically losses collagen. Extracellular (EC) Superoxide dismutase (SOD), also known as SOD3 is the major SOD in the extracellular matrix of the tissues, and is well known to maintain the redox homeostasis and matrix components of such tissues. However, the role of EC-SOD in aging-associated reductions of skin thickness and collagen production is not well studied. In this study, we compared the histological differences in the dorsal skin of EC-SOD overexpressing transgenic mice (SOD3) of different age-group with wild-type (WT) mice, and also determined the underlying signaling mechanism. Our data showed that the skin thickness in SOD3 mice significantly increased with age compared to WT male mice. Further, SOD3 promoted collagen production via activation of AMPK and Nrf2/HO-1 in aged mice. Interestingly, subcutaneous injection of adeno-associated virus overexpressing EC-SOD exhibited increased skin thickness and collagen expression. Furthermore, combined recombinant EC-SOD and dihydrotestosterone (DHT) treatment synergistically elevated collagen production via activation of TGF-β in human dermal fibroblasts. Altogether, these results demonstrated that EC-SOD prevents skin aging by promoting collagen production in vivo and in vitro. Therefore, we propose that EC-SOD may be a potential therapeutic target for anti-aging in the skin.