Lifelong SIRT-1 overexpression attenuates large artery stiffening with advancing age.

Advanced age is accompanied by aortic stiffening that is associated with decreased vascular expression of sirtuin-1 (SIRT-1). Interventions that increase SIRT-1 expression also lower age-related aortic stiffness. Therefore, we sought to determine if lifelong SIRT-1 overexpression would attenuate age-related aortic stiffening. Aortic pulse wave velocity (PWV) was assessed from 3-24 months in SIRT-1 transgenic overexpressing (SIRT) and wild-type (WT) mice. To determine the role of aortic structural changes on aortic stiffening, histological assessment of aortic wall characteristics was performed. Across the age range (3-24 mo), PWV was 8-17% lower in SIRT vs. WT (P<0.05). Moreover, the slope of age-related aortic stiffening was lower in SIRT vs. WT (2.1±0.2 vs. 3.8±0.3 cm/sec/mo, respectively). Aortic elastin decreased with advancing age in WT (P<0.05 old vs. young WT), but was maintained in SIRT mice (P>0.05). There was an age-related increase in aortic collagen, advanced glycation end products, and calcification in WT (P<0.05 old vs. young WT). However, this did not occur in SIRT (P>0.05). These findings indicate that lifelong SIRT-1 overexpression attenuates age-related aortic stiffening. These functional data are complemented by histological assessment, demonstrating that the deleterious changes to the aortic wall that normally occur with advancing age are prevented in SIRT mice.