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

Study Overview
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Brief Summary
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This project aims to assess the impact of chronic micro-inflammation on age-related loss of muscle (sarcopenia) and bone (osteopenia). The hypothesis is that chronic micro-inflammation and oxidative stress, which prevalence increases during ageing, may participate in the pathogenesis of both sarcopenia and osteopenia.

Detailed Description
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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.

Official Title
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Chronic Micro-inflammation and Bone and Muscular Status in Elderly

Conditions
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Age-related Degenerated Disease

Intervention / Treatment
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* Other: Measurement of muscle protein synthesis using stable isotopes and muscle biopsies.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Body mass index 21 BMI 30 kg/m2 Affiliated to National Health Insurance Subject giving his written informed consent Subject considered as normal after clinical examination and medical questionnaire. Exclusion Criteria: Positive serologies to HIV or HCV, determined on blood samples Previous medical and/or surgery judged by the investigator as incompatible with this study Chronic pathologies : Diabetes, cardiovascular diseases, cancer, chronic inflammation diseases, renal, pulmonary impairments Reported xylocaïne allergy Osteoporosis Prostate hypertrophy Glaucoma Heavy consumer of alcohol Practising intensive physical exercise Being under someone's supervision Refusal to be registered on the National Volunteers Data file Dietary habits unreliable to controlled food intake Being in exclusion on the National Volunteers Data file

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | at week 0 and week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Splanchnic extraction of amino acids, bone metabolism, muscular strength, global metabolism and quality of life. |  | at week 0 and week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ageing, Inflammation, Muscle protein synthesis, Osteopenia, Sarcopenia