Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years

Study Overview
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Brief Summary
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Women have a natural protection that gives them greater longevity. One hypothesis most commonly used is the estrogen protection in the premenopausal period. However many studies of various forms of hormone replacement therapy proved ineffective in promoting additional protection for women. Thus, it is discussed other ways of protection associated with longevity in women. Of these, the sirtuin system was found in several animal studies to be associated with longevity. This system also showed, through the involvement of several metabolic pathways, an important protection against the process of atherosclerosis. But the activity of this system in humans is unknown and if it is more active in women than in men. The study's main objectives are to analyze this system in healthy 24 women and 24 men aged 55 to 65 years, and their influence on the main metabolic pathways related to longevity and the process of atherosclerosis. The research protocol includes analysis of the influence of sirtuin (SIRT1) in vascular reactivity, lipid profile, antioxidant capacity, markers of inflammation and homeostasis, before and after the interventions with caloric restriction or resveratrol administration. It is expected of this study mechanistic conclusion for longevity and possible clinical applications in the mechanism of atherosclerosis prevention.

Detailed Description
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After a washout period of 15 days without medication, men and women will be randomized to the group of calorie restriction or resveratrol so that in 24 individuals (12 women and 12 men) will be given a hypocaloric diet (1000 calories per day) and the remaining 24 individuals (12 women and 12 men), a daily pill of 500mg of resveratrol. In the two moments, after the washout period and before the intervention (baseline) and after 30 days of intervention (final) will evaluate the clinical, laboratory and vascular reactivity of all subjects.

Official Title
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Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years.

Conditions
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Vascular System Injuries, Lipid Metabolism Disorders, Endothelial Disfunction

Intervention / Treatment
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* Drug: Resveratrol
* Behavioral: Caloric restriction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical history, physical examination and electrocardiogram normal Exclusion Criteria: premenopausal women (less than 1 year of natural amenorrhea) Body mass index ≥ 35 kg/m2 Smoking Severe hypertension (diastolic blood pressure ≥ 110 mmHg) Severe dyslipidemia (triglycerides ≥ 500mg/dL, total cholesterol ≥ 300mg/dL) Diabetes Previous using previous statins or hormone replacement therapy. Other exclusion criteria are: chronic renal failure (serum creatinine ≥ 2.0 mg / dl), hepatic, endocrine, hematologic, respiratory or metabolic clinically significant.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: men with resveratrol<br>12 men will receive a pill with 500mg of resveratrol daily for 30 days | Drug: Resveratrol<br>* 1 pill daily containing 500 mg/d of resveratrol for 30 days<br>|
| Experimental: women with resveratrol<br>12 women will receive a pill with 500mg of resveratrol daily for 30 days | Drug: Resveratrol<br>* 1 pill daily containing 500 mg/d of resveratrol for 30 days<br>|
| Active Comparator: men with caloric restriction<br>12 men will follow a 1000 calories per day diet for 30 days | Behavioral: Caloric restriction<br>* Diet of 1000kcal per day for 30 days<br>|
| Active Comparator: women with caloric restriction<br>12 women will follow a 1000 calories per day diet for 30 days | Behavioral: Caloric restriction<br>* Diet of 1000kcal per day for 30 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Direct Evaluation of the Sirtuin 1 Gene Expression | The Sirtuin 1 gene expression was measured by real time PCR in peripheric blood. Unit of measure was arbitrary unit. Arbitrary unit was relative to the control gene expression (control gene = 1). | 30 days post-treatment | 
| Sirtuin | Sirtuin plasma levels before and 30 days post-treatment | 30 days post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of the Sirtuin 1 System on Lipid Profile, Glucose, and C-reactive Protein. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - serum HDL, LDL, lipoprotein(a), C reactive protein, glucose. | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Apolipoproteins AI and B. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - apolipoproteins AI and B | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Estradiol | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estradiol | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Platelet Aggregation. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - platelet aggregation by ADP and norepinephrine. | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Biomarkers | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - non-esterified fatty acids, insulin, luteinizing hormone, follicle stimulating hormone. | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Estrone and Norepinephrine. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estrone, norepinephrine. | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Receptor for Advanced Glycation End Products (RAGE) Gene Expression | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: RAGE gene expression Arbitrary unit was relative to the control gene expression (control gene = 1) | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Thromboelastography Clot Formation. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -dynamics of clot formation: clot onset time and clot complet | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Thromboelastography. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - slope of clot formation dynamics | 30 days post-treatment | 
| Influence of the Sirtuin 1 System on Max Elasticity of Clot on Thromboelastography. | For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -max elasticity of clot on thromboelastography | 30 days post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sirtuin, atherosclerosis, longevity, calorie restriction, resveratrol, vascular reactivity