Caloric restriction is an established intervention, of which anti-aging effects are scientifically proven. It has pleiotropic effects on the cardiovascular system: vascular protection, improvement of myocardial ischemic tolerance and retardation of cardiac senescence. First, increasing evidence from both experimental and clinical studies supports the concept that "a man is as old as his arteries". Caloric restriction could prevent the progression of atherosclerosis and vascular aging through direct and indirect mechanisms. Second, the hearts of senescent animals are more susceptible to ischemia than those of young animals. We demonstrated that short-term and prolonged caloric restriction confers cardioprotection against ischemia/reperfusion injury in young and aged rodents. Furthermore, we showed that the increase in circulating adiponectin levels and subsequent activation of adenosine monophosphate-activated protein kinase are necessary for the cardioprotection afforded by short-term caloric restriction. In contrast, the mechanisms by which prolonged caloric restriction confers cardioprotection seem more complicated. Adiponectin, nitric oxide synthase and sirtuin may form a network of cardiovascular protection during caloric restriction. Recently, by using genetically engineered mice, we found that, in addition to endothelial nitric oxide synthase, neuronal nitric oxide synthase plays an essential role in the development of cardioprotection afforded by prolonged caloric restriction. Third, long-term caloric restriction has cardiac-specific effects that attenuate the age-associated impairment seen in left ventricular diastolic function. It is possible that long-term caloric restriction partially retards cardiac senescence by attenuating oxidative damage in the aged heart. Overall, we strongly believe that caloric restriction could reduce morbidity and mortality of cardiovascular events in humans. Geriatr Gerontol Int 2011; 11: 143-156.

BACKGROUND:Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner.

METHODS:Forty-five women were randomly assigned to four interventions:"placebo ingestion"(n = 11),"curcumin ingestion"(n = 11),"exercise training with placebo ingestion"(n = 11), or"exercise training with curcumin ingestion"(n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms.

RESULTS:There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P<0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P<0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group.

CONCLUSIONS:These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.

Bone marrow stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium. Despite initial excitement, recent clinical trials using non-homogenous stem cells preparations showed variable and mixed results. Selected CD133(+) hematopoietic stem cells are candidate cells with high potential. Herein, we report the one-year safety analysis on the initial 20 patients enrolled in the COMPARE-AMI trial, the first double-blind randomized controlled trial comparing the safety, efficacy, and functional effect of intracoronary injection of selected CD133(+) cells to placebo following acute myocardial infarction with persistent left ventricular dysfunction. At one year, there is no protocol-related complication to report such as death, myocardial infarction, stroke, or sustained ventricular arrhythmia. In addition, the left ventricular ejection fraction significantly improved at four months as compared to baseline and remained significantly higher at one year. These data indicate that in the setting of the COMPARE-AMI trial, the intracoronary injection of selected CD133(+) stem cells is secure and feasible in patients with left ventricle dysfunction following acute myocardial infarction.