Implication of Metabolic and Genomic Modifications in Elderly Subjects

Study Overview
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Brief Summary
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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.

Official Title
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Implication of Metabolic and Genomic Modifications in Elderly Subjects

Conditions
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Insulin Sensitivity, Aging

Intervention / Treatment
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* Drug: euglycemic hyperinsulinemic clamp
* Procedure: muscle biopsy
* Device: indirect calorimetry


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Problematic aging<br> | Drug: euglycemic hyperinsulinemic clamp<br>* Insulin perfusion at 1 mU.kg-1.min-1 Glucose perfusion to maintain euglycemia at 5,0 ± 0,5 mmol/l Blood tests<br>Procedure: muscle biopsy<br>* 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<br>Device: indirect calorimetry<br>* energy expenditure measurement<br>|
| Experimental: successful aging<br> | Drug: euglycemic hyperinsulinemic clamp<br>* Insulin perfusion at 1 mU.kg-1.min-1 Glucose perfusion to maintain euglycemia at 5,0 ± 0,5 mmol/l Blood tests<br>Procedure: muscle biopsy<br>* 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<br>Device: indirect calorimetry<br>* energy expenditure measurement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of metabolic profile (lipid metabolism and energy expenditure) and insulin sensitivity based on the aging quality |  | 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | one day | 
| Gene expression in muscle tissue by Global transcriptome analysis by DNA Chip |  | one day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin sensitivity, aging, lipid metabolism, hyperinsulinemic clamp, gene expression, sirtuins