Nutrition
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It has been well documented that as individuals age, body composition changes, even in the absence of changes in body weight. Studies have shown that fat mass increases and muscle mass decreases with age. However, it is unclear why such changes occur. ⋯ Although long-term longitudinal studies are lacking, most cross-sectional studies or short-term longitudinal studies show a reduction in RMR with aging that cannot be explained by changes in body composition including loss in fat-free mass, where the latter includes atrophy or decreases in the mass of high metabolic rate organs. There is indirect evidence suggesting that the metabolic rate of individual organs is lower in older compared with younger individuals. With aging, we conclude that reductions in the mass of individual organs/tissues and in tissue-specific organ metabolic rate contribute to a reduction in RMR that in turn promotes changes in body composition favoring increased fat mass and reduced fat-free mass.
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Cachexia is a devastating syndrome of body wasting that is associated with multiple common chronic diseases including cancer, chronic kidney disease, and chronic heart failure. These underlying diseases are associated with increased levels of inflammatory cytokines and result in anorexia, increased resting energy expenditure, and loss of fat and lean body mass. Prior experiments have implicated the central melanocortin system in the hypothalamus with the propagation of these symptoms of cachexia. ⋯ In addition, small molecule antagonists of the melanocortin-4 receptor continue to be introduced, including ones with oral bioavailability. These developments generate optimism that melanocortin antagonism will be used to treat humans with disease-associated cachexia. However, to date, human application has remained elusive and it is unclear when we will know whether humans with cachexia would benefit from treatment with these compounds.