Human Muscle Gene Expression Profiles in Young and Old Men (CERA)

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.

Study Overview

• Status: Completed
• Conditions: Sarcopenia; Elderly
• Intervention / Treatment: Other: Skeletal muscle aging

• Study Type: Observational
• Enrollment (Actual): 41

Contacts and Locations

Study Locations

• France
  • Saint-etienne, France, 42000
    • CHU de Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Young : students of the Saint-Etienne's university. Old : men who participate in the PROOF study

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Fondation des Caisses d'Epargne Rhône-Alpes
• Investigators: Study Chair: Daniel BECHET, PhD, INRA Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: July 29, 2008
• First Submitted That Met QC Criteria: July 29, 2008
• First Posted (Estimate): July 30, 2008

Study Record Updates

• Last Update Posted (Estimate): June 11, 2009
• Last Update Submitted That Met QC Criteria: June 9, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Healthy volunteers; Biopsy; Aging; Genetic markers; Skeletal muscle; Gene expression regulation; Molecular biology; Young and old men
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Sarcopenia
• Other Study ID Numbers: 0708102; 2008-A00374-51