The hormone factory skin never sleeps or Methusalem drugs and other ancient friends, revisited!

the “antidiabetic” drug metformin could be useful as an addon therapy to methotrexate for the treatment of psoriasis and, perhaps, for rheumatoid arthritis as well. Biochemical data suggest that both drugs may share a common cellular target, the AMP-activated protein kinase (AMPK). This enzyme is a master regulator of metabolism and controls a number of downstream targets, e.g., important for cellular growth or function in many tissues including T-lymphocytes. The authors explain that clinical observations as well as experimental results argue for anti-inflammatory, antineoplastic and antiproliferative activities of metformin and a case-control study suggests that the drug reduces the risk for psoriasis. They discuss that patients with psoriasis have higher risk of metabolic syndrome, type 2 diabetes and cardiovascular mortality. Metformin has proven efficacy in the treatment of prediabetes and leads to a pronounced and sustained weight loss in overweight individuals. The authors expect that addition of metformin to methotrexate can lead to positive effects with respect to the PASI score, reduction of the weekly methotrexate dose and of elevated cardiovascular risk factors in patients with metabolic syndrome and psoriasis. For several reasons they suggest that only male, overweight patients are to be included in a pilot trial. They state that on the other side of the coin are concerns that the gastrointestinal side effects of metformin are intolerable for patients under low dose, intermittent methotrexate therapy. Metformin has another side effect, namely interference with vitamin B 12 and folate metabolism, leading to elevated homocysteine serum levels. The authors explain that, as patients must receive folate supplementation and will be controlled with respect to their B 12 status increased hematological toxicity is unlikely to result. In the third paper, M. Julie Thornton summarizes our present understanding of the relevance of estrogens for aging skin. She explains that estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. The author states that estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair EDitor’s cornEr