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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
48
1 pill daily containing 500 mg/d of resveratrol for 30 days
Diet of 1000kcal per day for 30 days
INCOR - Heart Institute
São Paulo, São Paulo, Brazil
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)".
Time frame: 30 days post-treatment
Sirtuin
Sirtuin plasma levels before and 30 days post-treatment
Time frame: 30 days post-treatment
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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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)"
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 30 days post-treatment
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