Sirtuin function in aging heart and vessels

Sirtuins, aging, and cardiovascular risks

“…As reported before, with age, the expression and activity of SIRT1 gradually decrease and in parallel oxidative stress, a major cause of atherosclerosis, increases (Cencioni et al 2015). Age-related loss of SIRT1 protein expression in human VSMC correlates with a loss of capacity for vascular repair, diminished stress response, and increased senescence (D'Onofrio et al 2015;Thompson et al 2014).…”

“…Recent biophysical data indicate that resveratrol interacts with and modulates SIRT1 activity via an allosteric mechanism (Cencioni et al 2015;Hubbard et al 2013;Sinclair and Guarente 2014); these findings interestingly indicate that micromolar levels of resveratrol are sufficient to exert vasculoprotective effects through SIRT1 action (Csiszar et al 2009;Della-Morte et al 2009;Pacholec et al 2010;Ungvari et al 2007;Yang et al 2013). However, some data have suggested that resveratrol seems more likely act through a complex indirect mechanism dependent on the inhibition of phosphodiesterases (PDE) paralleled by AMPK activation (Beher et al 2009;Cencioni et al 2015;Park et al 2012;Yang et al 2013). Furthermore, resveratrol has been further shown to protect coronary endothelial cells against oxidative stress: in fact, it may stimulate in a dose-dependent manner SIRT1 deacetylase activity by increasing its binding affinity to both the acetylated substrate and NAD + (Howitz et al 2003).…”

“…It will be important to develop experimental models in which the levels of oxidative stress and the activities of sirtuins can be precisely modulated to determine how sirtuins have a causative role in lifespan extension. Also, the role of sirtuins in the cardiovascular system has been investigated (Cencioni et al 2015;D'Onofrio et al 2015;Pantazi et al 2013), and sirtuins appear to have a prominent role in cardiovascular biology and may regulate aspects of cardiovascular health and age-dependent CVDs.…”

“…Resveratrol, a polyphenolic antioxidant found in red wine, activating SIRT1 (Villalba and Alcain 2012;Wallerath et al 2002) prevents oxidative stress and coronary VSMC proliferation inhibiting extracellular signal regulated kinase (ERK) activation (Chong et al 2012;El-Mowafy et al 2008). Recent biophysical data indicate that resveratrol interacts with and modulates SIRT1 activity via an allosteric mechanism (Cencioni et al 2015;Hubbard et al 2013;Sinclair and Guarente 2014); these findings interestingly indicate that micromolar levels of resveratrol are sufficient to exert vasculoprotective effects through SIRT1 action (Csiszar et al 2009;Della-Morte et al 2009;Pacholec et al 2010;Ungvari et al 2007;Yang et al 2013). However, some data have suggested that resveratrol seems more likely act through a complex indirect mechanism dependent on the inhibition of phosphodiesterases (PDE) paralleled by AMPK activation (Beher et al 2009;Cencioni et al 2015;Park et al 2012;Yang et al 2013).…”

“…During the lifespan, the heart may be exposed to a large number of different stresses, like hypertrophic stress or apoptosis (Cencioni et al 2015). SIRT1 has been confirmed also as a key factor in myocardial hypertrophy; low to moderate SIRT1 heart expression (2.5-to 7.5-fold over endogenous levels) was found to be protective against age-dependent cardiac hypertrophy, apoptosis, and consequent left ventricular dysfunction, whereas SIRT1 overexpression (12.5-fold) induced dilatation, hypertrophy, and cardiac failure (Alcendor et al 2007;Ma et al 2010;Yang et al 2013).…”