Implication of Metabolic and Genomic Modifications in Elderly Subjects (COMPALICLAMP)

• Gene expression in muscle tissue by quantitative RT-PCR: genes involved in the carbohydrates and lipids metabolism (lipid carriers, PPARs), 7 sirtuins isoforms and of their target genes (NFkB, PGC1a) [ Time Frame: one day ] [ Designated as safety issue: No ]
• Gene expression in muscle tissue by Global transcriptome analysis by DNA Chip [ Time Frame: one day ] [ Designated as safety issue: No ]

An increase of longevity and of the number of men and women older than 60 years old is observed in most industrialized countries. Aging is a complex, multifactorial and continuous process involving physical and biological modifications such as a notably decrease in glucose tolerance and type 2 diabetes risk. Insulin sensitivity follow-up during aging is difficult mainly because of many confounding factors (environment, lifestyle).

In 2006, SUVIMAX 2 study began, based on the monitoring of volunteers who participated in former SUVIMAX study (1994-2003). This study was a randomised trial which was designed to study the link between a low antioxidant intake and risk of cancer or ischemic heart disease. The subjects recently had a health check-up including complete information about their diet, physical and neurosensory status. Based on these data, a score was established to classify subjects according to their quality of aging ("successful aging versus "problematic aging") These volunteers, who undertook a 13-year follow-up (dietary and medical status), constitute the reference population to determine the mechanisms involved in the insulin resistance development in aging.

The purpose of our research work is to determine whether the quality of aging could influence insulin sensitivity, by studying metabolic profile and change in gene expression (genes involved in glucose metabolism and metabolic senescence in muscle tissue) during aging.

• Insulin Sensitivity
• Aging

• Drug: euglycemic hyperinsulinemic clamp

  Insulin perfusion at 1 mU.kg-1.min-1

  Glucose perfusion to maintain euglycemia at 5,0 ± 0,5 mmol/l

  Blood tests

• Procedure: muscle biopsy

  Gene expression in muscle tissue will be studied with two approaches :

  • Candidate gene approach by quantitative RT-PCR : genes involved in the carbohydrates and lipids metabolism including lipid oxidation in muscle (lipid carriers, PPARs), expression of 7 sirtuins isoforms as well as some of their target genes (NFkB, PGC1a)
  • Global transcriptome analysis by DNA Chip
• Device: indirect calorimetry
  energy expenditure measurement

• Experimental: Problematic aging
  Interventions:

  • Drug: euglycemic hyperinsulinemic clamp
  • Procedure: muscle biopsy
  • Device: indirect calorimetry
• Experimental: successful aging
  Interventions:

  • Drug: euglycemic hyperinsulinemic clamp
  • Procedure: muscle biopsy
  • Device: indirect calorimetry

Inclusion Criteria:

• Volunteers from the cohort aging SUVIMAX 2
• Men and Women
• over 60 years
• BMI between 18 and 35 kg/m2 (including terminals)
• Normal medical check up
• Blood pressure < 140/90 mmHg
• Normal glycemia, lipid profile
• sedentary or moderate physical activity (maximum 4 hours per week)

Exclusion Criteria:

• Biological results or anormal chek-up
• medical or surgical history not compatible with study
• severe digestive, cardiovascular, renal, liver or tumor disorders history in the 5 last years
• infectious or inflammatory disease within 2 months
• surgical history within 3 months
• bood donation within 2 months
• coagulation disease, anticoagulant or antiplatelet agents (aspirin ...) treatment
• xylocaïn allergy
• claustrophobia
• Drug that could affect insulin sensitivity (beta blockers, lipid lowering, oral antidiabetics, insulin, , steroids)