Relationships Between Quality of Ageing and Age-related Degenerated Disease (Compalimage)

• Isotopic enrichments in expired gas, in plasma cetoisocaproate and in free or protein-bound leucine in muscle will be measured to determine proteolysis and proteosynthesis rate of muscle proteins. [ Time Frame: at week 0 and week 6 ] [ Designated as safety issue: Yes ]
  

• Splanchnic extraction of amino acids, bone metabolism, muscular strength, global metabolism and quality of life. [ Time Frame: at week 0 and week 6 ] [ Designated as safety issue: Yes ]
  

Other: Measurement of muscle protein synthesis using stable isotopes and muscle biopsies.

Measurement of muscle protein synthesis using stable isotopes and muscle biopsies.

Isotopes are :

(13C)bicarbonate (0.09 mg/kg fat-free mass) and L(1-13C)leucine (1.3 mg/kg fat-free mass) (intravenous way) L-(5,5,5 2H3) leucine(0.09 µmoles/(kg de fat-free mass.min) (oral way)

In order to explore the effect of a moderate chronic inflammation on skeletal muscle function and protein metabolism and on bone status, two groups of 16 subjects each will be selected according to their inflammatory status ie non-inflamed versus micro-inflamed. The volunteers will be sampled twice at week 0 and week 6 in order to quantify plasma concentration of C reactive protein (CRP) using the ultra sensitive assay. The subjects exhibiting CRP lower than 1 mg/l twice will be included in the non-inflamed group and the subjects exhibiting CRP higher than 3 and lower than 15 mg/l will be included in the micro-inflamed group.

During the two weeks before the metabolic studies dietary intakes, DEXA, muscle function, VO2 max and biomarkers of bone remodelling will be assessed. Volunteers will then be submitted to a diet controlled for its protein content, for 4 days (1 g protein/kg/day and 30 kcal/kg/day) before metabolic investigations. One day before, urine will be collected for metabolomics. On the day of metabolic investigations, after an overnight fast, blood samples will be collected for albumin, fibrinogen, inflammatory cytokine and adipokine determination. Then, the subjects will be perfused with L-[1-13C] leucine for 8 hours (post absorptive sate then post prandial satte) during which expired gas and blood samples will be taken, as well as 2 muscle biopsies. Isotopic enrichments in expired gas, in plasma cetoiscaproate and in free or protein-bound leucine in muscle will be measured to determine proteolysis and proteosynthesis rate of muscle proteins.