The anti-ageing molecule sirt1 mediates beneficial effects of cardiac rehabilitation

Abstract

Background: An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view. Results: A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation. In fifty elderly HF patients with preserved ejection fraction (HFpEF), levels of sirtuin 1 (Sirt1) in peripheral blood mononuclear cells (PBMCs) and of its targets, the antioxidants catalase (Cat) and superoxide dismutase (SOD) in serum were measured before (Patients, P) and at the end of the CRP (Rehabilitated Patients, RP), showing a rise of their activities after rehabilitation. Endothelial cells (ECs) were conditioned with serum from P and RP, and oxidative stress was induced using hydrogen peroxide. An increase of Sirt1 and Cat activity was detected in RP-conditioned ECs in both the absence and presence of oxidative stress, together with a decrease of senescence, an effect not observed during Sirt1 and Cat inhibition.

Controversial Impact of Sirtuins in Chronic Non-Transmissible Diseases and Rehabilitation Medicine

“…In this condition, a strong reduction of senescence biomarkers was observed compared to controls [50]. To better understand the role of Sirt1 in this process, Sirt1 was inhibited determining an increase of EC senescence and a decrease in Cat activity [50]. These data clearly contribute the evidence that Sirt1 is activated during CR in CHF patients, however, further experiments on a larger cohort of subjects should be necessary to better understand the contribution of Sirt1 in CHF.…”

“…Specifically, ECs were challenged with serum of HF patient taken at the end of rehabilitation training. In this condition, a strong reduction of senescence biomarkers was observed compared to controls [50]. To better understand the role of Sirt1 in this process, Sirt1 was inhibited determining an increase of EC senescence and a decrease in Cat activity [50].…”

“…Notably, in untrained CHF patients, Sirt1 in significantly down-regulated, a phenomenon that has been seen also in cardiac hypertrophy in the presence of pressure overload [49]. In a recent study, the beneficial effect of exercise in CHF patients has been investigated throughout and at the end of an intense rehabilitation program by collecting blood samples to evaluate Sirt1, superoxide dismutase (SOD) and antioxidant catalase (Cat), activity in peripheral blood mono-nucleated cells and in plasma samples respectively [50]. The result of this trial showed an increase of Sirt1 and Cat compared to control levels, while SOD was reduced [50].…”

“…In a recent study, the beneficial effect of exercise in CHF patients has been investigated throughout and at the end of an intense rehabilitation program by collecting blood samples to evaluate Sirt1, superoxide dismutase (SOD) and antioxidant catalase (Cat), activity in peripheral blood mono-nucleated cells and in plasma samples respectively [50]. The result of this trial showed an increase of Sirt1 and Cat compared to control levels, while SOD was reduced [50]. Additionally, this study evaluated the effect of patients' serum on the senescence process of endothelial cells (EC).…”

Endothelium at a Glance

“…On the other hand, cyclic stretch and angiotensin II (AngII) have been shown to increase tubulin deacetylation and tubular reorganization, predisposing to the development of cardiovascular diseases [63]; potential role on the AngII type 1 receptor antagonist in positively affecting endothelial microtubular organization has been implicated [63]. The longevity regulator sirtuin 1 (SIRT1), a potential therapeutic target [64], has been implicated in tubulin deacetylation and the regulation of microtubule function [63].…”