Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

Abstract

SummaryWe 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 (O2−) 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 O2− 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 O2− 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.

Reductive carboxylation is a major metabolic pathway in the retinal pigment epithelium

“…NAD + declines with age (47,51), and supplementation with NAD + precursors can delay aging, liver disease, and vascular dysfunction (52)(53)(54). NAD + precursors, such as nicotinamide riboside, can be used safely in humans (55,56).…”

NAD and the aging process: Role in life, death and everything in between

“…In another study, 8 weeks of NMN supplementation restored arterial SIRT1 activity and ameliorated age-associated endothelial dysfunction and large elastic artery stiffening in mice. These improvements restored nitric oxide bioavailability, reduced oxidative stress, and promoted complete or partial normalization of structural proteins in the arterial wall (de Picciotto et al, 2016). …”

Nutrition and other lifestyle influences on arterial aging

“…There is, however, some evidence in support of other activators of the SIRT-1 network, such as nutraceuticals that boost NAD + (the cellular trigger for SIRT-1 activity). For example, supplementation with nicotinamide mononucleotide (NMN), a metabolic precursor to NAD + , restores endothelial function and decreases arterial stiffness (de Picciotto et al, 2016), and clinical trials investigating the effects of nicotinamide riboside (NR, a similar compound found in milk and yeast-derived foods) on various physiological parameters, including arterial function, are currently underway (clinicaltrials.gov).…”