Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Issue 3 (11th March 2016)

• Record Type: Journal Article
• Authors: de Picciotto, Natalie E.; Gano, Lindsey B.; Johnson, Lawrence C.; Martens, Christopher R.; Sindler, Amy L.; Mills, Kathryn F.; Imai, Shin‐ichiro; Seals, Douglas R.
• Is Part Of: Aging cell. Volume 15:Issue 3(2016)
• Page Start: 522
• Page End: 530
• Publication Date: 2016-03-11
• Subjects: arterial stiffness -- endothelial dysfunction -- NAD+ -- oxidative stress -- SIRT1; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12461
• Languages: English
• ISSNs: 1474-9718

Abstract

Summary: We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD + intermediate, increases arterial SIRT1 activity and reverses age‐associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium‐dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)‐mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age‐associated impairment in EDD was restored in OC by the superoxide ( O 2 − ) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s −1 vs. 337 ± 3 cm s −1 ) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O 2 − production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen‐I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO‐mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s −1 ) and EM (3694 ± 315 kPa), normalized O 2 − production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen‐I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.