The loss of skeletal muscle mass with aging has been attributed to an impaired muscle protein synthetic response to food intake. Therefore, nutritional strategies are targeted to modulate postprandial muscle protein accretion in the elderly. The purpose of this study was to assess the impact of protein administration during sleep on in vivo protein digestion and absorption kinetics and subsequent muscle protein synthesis rates in elderly men. Sixteen healthy elderly men were randomly assigned to an experiment during which they were administered a single bolus of intrinsically l-[1-(13)C]phenylalanine-labeled casein protein (PRO) or a placebo (PLA) during sleep. Continuous infusions with l-[ring-(2)H(5)]phenylalanine and l-[ring-(2)H(2)]tyrosine were applied to assess in vivo dietary protein digestion and absorption kinetics and subsequent muscle protein synthesis rates during sleep. We found that exogenous phenylalanine appearance rates increased following protein administration. The latter stimulated protein synthesis, resulting in a more positive overnight whole body protein balance (0.30 ± 0.1 vs. 11.8 ± 1.0 μmol phenylalanine·kg(-1)·h(-1) in PLA and PRO, respectively; P < 0.05). In agreement, overnight muscle protein fractional synthesis rates were much greater in the PRO experiment (0.045 ± 0.002 vs. 0.029 ± 0.002%/h, respectively; P < 0.05) and showed abundant incorporation of the amino acids ingested via the intrinsically labeled protein (0.058 ± 0.006%/h). This is the first study to show that dietary protein administration during sleep is followed by normal digestion and absorption kinetics, thereby stimulating overnight muscle protein synthesis. Dietary protein administration during sleep stimulates muscle protein synthesis and improves overnight whole body protein balance. These findings may provide a basis for novel interventional strategies to attenuate muscle mass loss.

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C3 is the central component of the complement system and activation of C3 via any of the three major activation pathways—the classical, the lectin and the alternative pathways—results in initiation of the terminal complement pathway and release of the anaphylatoxin C3a. Both terminal pathway activation and signalling of C3a and its inactivation product C3a-desarg via the C3a receptor and C5a-like receptor 2, respectively, can induce inflammatory, immunomodulatory and metabolic responses. C3 has been implicated in metabolic disorders, notably adiposity, dyslipidaemia, insulin resistance, liver dysfunction and diabetes, and C3 is increasingly recognised as a cardiometabolic risk factor. C3 may play a role in the macrovascular, as well as microvascular, complications of diabetes. Moreover, C3 may interact with the coagulation system and as such also contribute to a procoagulant, hypofibrinolytic and, ultimately, prothrombotic state. Recent data suggest a diabetes-dependent incorporation of C3 into fibrin clots, with concomitant effects on clot characteristics. Taken together, epidemiological and experimental evidence concordantly point to a role of complement C3 in metabolic, atherosclerotic/atherothrombotic and microangiopathic processes and further research should be directed towards the elucidation of complement function and activation in cardiometabolic disorders.

The alternative pathway of complement activation is highly reactive and can be activated spontaneously in the vasculature. Activation may contribute to vascular damage and development of cardiovascular disease (CVD). We aimed to investigate functional components of the alternative pathway in cardiovascular risk. We studied 573 individuals who were followed-up for seven years. At baseline, we measured the enhancer properdin; the rate-limiting protease factor D (FD); and a marker of systemic activation, Bb. Using generalised estimating equations, we investigated their longitudinal associations with cardiovascular events (CVE, N=89), CVD (N=159), low-grade inflammation (LGI), endothelial dysfunction (ED) and carotid intima-media thickness (cIMT). Furthermore, we investigated associations with incident CVE (N=39) and CVD (N=73) in 342 participants free of CVD at baseline. CVE included myocardial infarction, stroke, cardiac angioplasty and/or cardiac bypass. CVD additionally included ischaemia on an electrocardiogram and/or ankle-brachial index < 0.9. In adjusted analyses, properdin was positively associated with CVE (per 1SD, longitudinal OR=1.36 [1.07; 1.74], OR for incident CVE=1.53 [1.06; 2.20]), but not with CVD. Properdin was also positively associated with ED (β=0.13 [95%CI 0.06; 0.20]), but not with LGI or cIMT. FD and Bb were positively associated with LGI (per 1SD, FD: β=0.21 [0.12; 0.29], Bb: β=0.14 [0.07; 0.21]), and ED (FD: β=0.20 [0.11; 0.29], Bb: β=0.10 [0.03; 0.18]), but not with cIMT, CVE or CVD. Taken together, this suggests that the alternative complement pathway contributes to processes of vascular damage, and that in particular a high potential to enhance alternative pathway activation may promote unfavourable cardiovascular outcomes in humans.