MAP kinase phosphatase-1 -a new player at the nexus between sarcopenia and metabolic disease

Abstract

Sarcopenia, which is defined by the loss of skeletal muscle mass, predisposes skeletal muscle to metabolicdysfunction which can precipitate metabolic disease. Similarly, overnutrition, which is a major health problem in modernsociety, also causes metabolic dysfunction in skeletal muscle and predisposition to metabolic disease. It is now theprevailing view that both aging and overnutrition negatively impact skeletal muscle metabolic homeostasis throughdeleterious effects on the mitochondria. Accordingly, interplay between the molecular pathways implicated in aging andovernutrition that induce mitochondrial dysfunction are apparent. Recent work from our laboratory has uncovered thestress-responsive mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) as a new player in the regulation ofmetabolic homeostasis in skeletal muscle and mitochondrial dysfunction caused by overnutrition. These observations raisethe intriguing possibility that MKP-1 may function as a common target in the convergence between sarcopenia andovernutrition in a pathophysiological pathway that leads to a loss of skeletal muscle mitochondrial function. With theincreasing aging population it will become more important to understand how MKP-1, and possibly other phosphatases, operate at the nexus between sarcopenia and metabolic disease. © Flach and Bennett.