Research Paper Volume 12, Issue 12 pp 11314—11324

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

Daniel R. Machin1, , Yauling Auduong1, , Venkateswara R. Gogulamudi1, , Yu Liu1, , Md. Torikul Islam2, , Lisa A. Lesniewski1,2,4, , Anthony J. Donato1,2,3,4, ,

  • 1 University of Utah, Department of Internal Medicine, Salt Lake City, UT 84132, USA
  • 2 University of Utah, Department of Nutrition and Integrative Physiology, Salt Lake City, UT 84112, USA
  • 3 University of Utah, Department of Biochemistry, Salt Lake City, UT 84132, USA
  • 4 VA Salt Lake City, GRECC, Salt Lake City, UT 84148, USA

Received: February 25, 2020       Accepted: April 28, 2020       Published: June 20, 2020
How to Cite

Copyright © 2020 Machin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 (SIRTTG) 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 SIRTTG vs. WT (P<0.05). Moreover, the slope of age-related aortic stiffening was lower in SIRTTG 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 SIRTTG 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 SIRTTG (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 SIRTTG mice.


AGE: advanced glycation end product; CR: caloric restriction; CVD: cardiovascular disease; eNOS: endothelial nitric oxide synthase; MMP: matrix metalloproteinase; NAD: nicotinamide adenine dinucleotide; NO: nitric oxide; PWV: pulse wave velocity; SIRT: sirtuin; SIRTTG: sirtuin-1 transgenic overexpressing; SOD: superoxide dismutase; TIMP: tissue inhibitor of matrix metalloproteinase; VAMC-SLC: Veteran's Affairs Medical Center-Salt Lake City; WAT: white adipose tissue; WT: wild-type.