Targeting oxidative stress for improving cardiovascular performance in the elderly

Oxidative stress is implicated in the pathophysiology of several cardiovascular diseases, as evidenced by correlation between oxidative stress markers and Heart Failure (HF) and by direct molecular evidence for an etiological role of reactive oxygen species (ROS). ROS play an important role in signalling processes, but their overproduction generates oxidative stress. Previous studies demonstrated that HF was associated with antioxidant deficit as well as increased oxidative stress. Furthermore, these changes correlated with the hemodynamic function, suggesting their role in the pathogenesis of cardiac dysfunction. An important mechanism involved in cellular cardiovascular response is represented by sirtuins. SIRT1 inhibition determines suppression of genes ac tivated by exposure to heat shock, on the contrary, SIRT1 activation enhances the heat shock response. Then the ability of SIRT1 to modulate stress resistance is multifaceted and not only linked to oxidative stress, but also to other stressful stimuli. Recently several studies have demonstrated the capability of physical activity to induce SIRT1 activity and, in turn, the ability of this enzyme to mediate the favourable antioxidant effects of the exercise training. Other agents able to induce SIRT1 activity have demonstrated some effects on cardiac function. Resveratrol supplementation has been shown to decrease cardiovascular risk factors, and the positive effect of resveratrol on training response and aerobic capacity in rats to be mediated via SIRT1. The future research should be addressed to better clarify the possible role of the antioxidants therapy in clinical studies, in particular defining a standardization of procedures, doses and duration of treatment.