Human Muscle Gene Expression Profiles in Young and Old Men

Study Overview
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Brief Summary
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To reach the goals of living longer in better medical conditions, many countries reach the same conclusion: new strategies have to be developed to avoid, or at least limit, the effects of age; this requires a better knowledge of the mechanisms of aging. Our project focuses on the loss of muscle mass associated with aging, called sarcopenia. Sarcopenia unavoidably leads to impaired mobility and poor balance, which contributes to loss of functional autonomy and to increased prevalence for severe falls. Skeletal muscle also plays a central role as a reserve for energy and amino acids. Hence, sarcopenia further triggers severe side metabolic effects such as frailty among elderly persons. The precise mechanisms of muscle aging are still mostly unknown, although many theories have been proposed. The present study aims at better understanding the mechanisms of skeletal muscle loss associated with aging. Using muscle biopsies from young and old subjects, the differential expression profiles of mRNA will be obtained through chips that will evaluate more than 39000 transcripts. On the same samples, proteomic analyses will involve two complementary approaches: (1) bidimensional electrophoresis (2DGE) coupled to mass spectrometry (MALDI-ToF) for dominant proteins; (2) Western-blot (more than 800 antibodies) targeting regulating proteins not detectable using 2DGE. Complementary histological studies (immunohisto-fluorescence, confocal microscopy) will specify the localisation of the major biomarkers in the muscle biopsies. The results of that research will have applications in the medium term and will lead to nutritional interventions to modulate specific metabolic pathways and improve the quality of life in the elderly.

Official Title
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Human Muscle Gene Expression Profiles in Young and Old Men

Conditions
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Elderly, Sarcopenia

Intervention / Treatment
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* Other: Skeletal muscle aging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Affiliated or beneficiary of a social security category Having signed the inform consent form Having signed the genetic consent form Exclusion Criteria: Antiaggregant platelet treatment Type 2 diabetes Body Mass Index > 25 Severe renal disease CRP > 10 Abnormal clotting test Allergies to local anesthetics

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 76 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Young<br>Young men 19-25 years old | Other: Skeletal muscle aging<br>* W1 - Blood test Maximal voluntary contraction of quadriceps Hydrostatic weighing W2 - Maximal metabolic test using a cycloergometer W3 - Muscular biopsy<br>|
| Old<br>old men 70-76 years old, who participate in the PROOF study (NCT 00759304) | Other: Skeletal muscle aging<br>* W1 - Blood test Maximal voluntary contraction of quadriceps Hydrostatic weighing W2 - Maximal metabolic test using a cycloergometer W3 - Muscular biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify the differential expression profiles (proteomics, transcriptomics) in skeletal muscle between young and old men |  | During biopsie (W3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To specify the localisation of the major biomarkers in the muscle biopsies. |  | During biopsie (W3) | 
| To compare muscular energy metabolic enzymatic activities between young and old men |  | during biopsie (W3) | 
| To compare the number of muscular stem cells between young and old men |  | during biopsie (W3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging, Biopsy, Skeletal muscle, Molecular biology, Genetic markers, Gene expression regulation, Young and old men, Healthy volunteers