Abstract
Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process. Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease. In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence. The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations. Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.
Highlights
Skin is the largest and the most visible organ of the human body
We have shown that Methylene blue (MB) at nanomolar concentration rescued abnormal nuclear and mitochondrial phenotypes, stimulated cell proliferation and delayed senescence in skin fibroblasts from patients with Hutchinson-Gilford progeria syndrome (HGPS, progeria), a rare genetic disorder of accelerated aging[13]
To evaluate the effectiveness of MB as an antioxidant, we first compared the effects of MB treatment with the effects of three other popular reactive oxygen species (ROS) scavengers, N-Acetyl-L-cysteine (NAC), MitoQ, and MitoTEMPO. (Supplemental Tables 1 and 2)
Summary
Skin is the largest and the most visible organ of the human body. Aged skin is biologically characterized by the flattening of the dermal-epidermal junction and a general atrophy of the extracellular matrix (ECM) with disorganized and reduced collagen and elastin[1, 2]. Extrinsic skin aging is an accelerated form due to exposure of the skin to sunlight and/or air pollution and is phenotypically demonstrated as dry, rough, pigmented and abraded skin especially in the face and hands They present with different clinical features, both types of skin aging are due in part to the oxidative damage caused by free radicals. The over-abundance of ROS decreases collagen synthesis and increases collagen breakdown by stimulating matrix metalloproteinase (MMP) expression, eventually causing the alterations of the dermal matrix[5, 6] Based on this ROS theory, an effective approach to delay skin aging is to externally supply antioxidants through skincare products to either suppress the production or neutralize the excess free radicals[6]. We have shown that MB at nanomolar concentration rescued abnormal nuclear and mitochondrial phenotypes, stimulated cell proliferation and delayed senescence in skin fibroblasts from patients with Hutchinson-Gilford progeria syndrome (HGPS, progeria), a rare genetic disorder of accelerated aging[13]
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