Slight chronic elevation of C-reactive protein is associated with lower aerobic fitness but does not impair meal-induced stimulation of muscle protein metabolism in healthy old men

Key pointsDevelopment of low grade inflammation has been correlated with sarcopenia in humans and shown to induce an anabolic resistance of muscle protein metabolism to dietary amino acid intake in an animal model. Low grade inflammation is clinically and routinely detected in humans by measurement of the plasma C-reactive protein level. In healthy elderly individuals presenting a slight but chronic elevation of C-reactive protein, we show that neither muscle, nor whole body protein metabolism was affected. By contrast, a decrease in aerobic fitness, an increase in abdominal fat mass and a post-prandial insulin resistance was detected. Our results show that the unique detection of chronic C-reactive protein elevation could predict a decrease in aerobic fitness and insulin resistance installation in elderly individuals but not muscle anabolic resistance to food intake. AbstractAgeing impairs the muscle anabolic effect of food intake, which may explain muscle loss and an increased risk of sarcopenia. Ageing is also associated with low grade inflammation (LGI), which has been negatively correlated with muscle mass and strength. In rodents, the muscle anabolic resistance observed during ageing and sarcopenia has been ascribed to the development of the LGI. We aimed to investigate this relationship in humans. We studied protein metabolism and physical fitness in healthy elderly volunteers with slight chronic C-reactive protein. Two groups of healthy elderly volunteers were selected on the presence (or not) of a chronic, slight, elevation of CRP (Control: <1; CRP+: >2mgl(-1) and <10mgl(-1), for 2 months). Body composition, short performance battery test, aerobic fitness and muscle strength were assessed. Whole body and muscle protein metabolism and the splanchnic extraction of amino acids were assessed using [C-13]leucine and [H-2]leucine infusion. The anabolic effect of food intake was measured by studying the volunteers both at the post-absorptive and post-prandial states. Slight chronic CRP elevation resulted in neither an alteration of whole body, nor skeletal muscle protein metabolism at both the post-absorptive and the post-prandial states. However, CRP+ presented a reduction of physical fitness, increased abdominal fat mass and post-prandial insulin resistance. Plasma cytokines (interleukin-1(,) interleukin-6, tumour necrosis factor ) and markers of endothelial inflammation (intercellular adhesion molecule, vascular cell adhesion molecule, selectins) were similar between groups. An isolated elevated CRP in healthy older population does not indicate an impaired skeletal muscle anabolism after food intake, nor an increased risk of skeletal muscle wasting. We propose that a broader picture of LGI (notably with elevated pro-inflammatory cytokines) is required to impact muscle metabolism and mass. However, an isolated chronic CRP elevation could predict a decrease in aerobic fitness and insulin resistance installation in elderly individuals.