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Mark E Cleasby, Pauline M Jamieson, and Philip J Atherton

Insulin resistance (IR) in skeletal muscle is a key defect mediating the link between obesity and type 2 diabetes, a disease that typically affects people in later life. Sarcopenia (age-related loss of muscle mass and quality) is a risk factor for a number of frailty-related conditions that occur in the elderly. In addition, a syndrome of ‘sarcopenic obesity’ (SO) is now increasingly recognised, which is common in older people and is applied to individuals that simultaneously show obesity, IR and sarcopenia. Such individuals are at an increased risk of adverse health events compared with those who are obese or sarcopenic alone. However, there are no licenced treatments for sarcopenia or SO, the syndrome is poorly defined clinically and the mechanisms that might explain a common aetiology are not yet well characterised. In this review, we detail the nature and extent of the clinical syndrome, highlight some of the key physiological processes that are dysregulated and discuss some candidate molecular pathways that could be implicated in both metabolic and anabolic defects in skeletal muscle, with an eye towards future therapeutic options. In particular, the potential roles of Akt/mammalian target of rapamycin signalling, AMP-activated protein kinase, myostatin, urocortins and vitamin D are discussed.