The role of adipose-derived extracellular vesicles in driving the impairment in skeletal muscle metabolic function and growth with ageing and obesity

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The decline in muscle mass and function (sarcopenia) and accompanying increase in adiposity with ageing is a major healthcare challenge, that drives frailty and the development of chronic inflammatory metabolic disorders including Type II Diabetes (T2D). The accumulation of intramuscular and intramyocellular fat exacerbates both the impairment of insulin sensitivity and muscle mass. Importantly, we have reported that exposure of human muscle to the secretome from obese (but not normal-weight) adipose tissue impairs muscle growth, particularly in elderly individuals, suggesting that pathological cross-talk between obese adipose tissue and muscle plays a central role in the exacerbation of sarcopenia.With the recent discovery of extracellular vesicles (EVs) as mediators of cellular cross-talk, capable of transporting cargo including small non-coding RNAs, we hypothesise that with ageing, obese adipose tissue releases pathological EVs that impair muscle growth and muscle metabolic function. The aim of this studentship is two-fold. Firstly, to characterise the small RNA cargo of these adipose EVs from lean and obese individuals, and secondly to determine the effect of adipose EVs on muscle growth and function to identify candidate pathways and drug targets for the development of therapeutics to combat sarcopenia.