Open AccessNicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice
Author(s) -
Picciotto Natalie E.,
Gano Lindsey B.,
Johnson Lawrence C.,
Martens Christopher R.,
Sindler Amy L.,
Mills Kathryn F.,
Imai Shinichiro,
Seals Douglas R.
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12461
Subject(s) - nicotinamide mononucleotide , oxidative stress , nitrotyrosine , medicine , endocrinology , elastin , arterial stiffness , endothelial dysfunction , peroxynitrite , pulse wave velocity , superoxide dismutase , nitric oxide , chemistry , nad+ kinase , biology , biochemistry , superoxide , nicotinamide adenine dinucleotide , nitric oxide synthase , blood pressure , pathology , enzyme
Summary We tested the hypothesis that supplementation of nicotinamide mononucleotide ( NMN ), a key NAD + intermediate, increases arterial SIRT 1 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 (a PWV , 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 SIRT 1 activity, measured by the acetylation status of the p65 subunit of NF κB, 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 SIRT 1 activity. Acute NMN incubation in isolated aortas increased NAD + threefold and manganese superoxide dismutase ( M n SOD ) by 50%. NMN supplementation may represent a novel therapy to restore SIRT 1 activity and reverse age‐related arterial dysfunction by decreasing oxidative stress.