Novel Strategies for Metformin as an Anti-aging Drug in Skin Aging

The skin aging process is caused by an interaction of epigenetic, genetic, and environmental factors. Thus, skin suffers from extrinsic and intrinsic factors enhancing this process. Both factors contribute to ROS formation in skin aging. ROS is necessary for intrinsic aging; it is produced mainly in mitochondria due to aerobic metabolic reactions. As for extrinsic aging, smoking, UV, and hyperglycemia lead to ROS generation. In skin aging process, generated excessive ROS activates MAPKs and thus induces NF-κB transcription factors. This activation inhibits TGF-β signaling pathway and increases MMPs expression, leading to decreased collagen synthesis and breakdown. Excess ROS related to aging-associated diseases also accelerates skin aging. On the other hand, metformin, an antidiabetic agent, via inactivating NF-kB, inhibits oxidative stress, ameliorates inflammatory reactions, improves mitochondrial function, and regulates cell death. Up-to-date evidence suggests that NF-kB signaling dysfunction and dysregulation are related to skin aging. There are current mechanisms and novel strategies for the therapeutic manipulation of NF-kB in treating skin aging. This chapter summarizes the current role of NF-kB in dermal aging, underlines the molecular mechanism of metformin in skin aging, attributes its effects to the modulation of NF-kB, and presents novel therapeutic approaches to skin aging through this modulation.