Preclinical mechanistic study

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

Natalie E de Picciotto, Lindsey B Gano, Lawrence C Johnson, Christopher R Martens, Amy L Sindler, Kathryn F Mills, Shin-Ichiro Imai, Douglas R Seals

Aging Cell · 2016 · 15(3):522–530

Original publication PubMed Full text on PMC

Study at a glance

Design: Preclinical intervention study comparing young and old mice with vascular functional and molecular assays
Population or model: Young and old mice; aged mice received NMN supplementation
Sample size: Multiple animal groups; see publication for experimental group sizes
Intervention: NMN supplementation in old mice; acute NMN incubation also studied in isolated aortas
Publication type: Preclinical animal study
Evidence class: preclinical-mechanistic
Research area: Vascular aging mechanisms
Trial registration: Not applicable.

Study endpoints

Endothelium-dependent dilation
Nitric-oxide-mediated dilation
Aortic pulse-wave velocity
Oxidative-stress markers
Collagen and elastin
Vascular SIRT1 activity
Aortic NAD+

Plain-language summary

This study examined vascular aging in mice and tested whether NMN could restore vascular function in old animals.

In aged mice, NMN improved endothelium-dependent dilation, reduced arterial stiffness and oxidative-stress measures, and altered vascular SIRT1, collagen and elastin-related markers toward values seen in younger mice.

These are substantial preclinical vascular findings, but they do not establish that NMN lowers cardiovascular risk or reverses arterial aging in people.

Key findings

NMN restored endothelium-dependent dilation in aged mice.
Aortic pulse-wave velocity and elastic modulus were reduced in treated old mice.
Oxidative-stress markers decreased and vascular SIRT1-related activity was restored.
Acute NMN exposure increased NAD+ in isolated aortic tissue.

Limitations

Mouse study only.
Vascular surrogate and molecular endpoints are not human cardiovascular events.
Animal dosing and tissue exposure may not reflect oral human supplementation.
Human trials are needed before clinical vascular claims can be made.

Funding and transparency

Funding

Supported by National Institutes of Health grants AG013038 and AG000279 to D.R.S. and AG024150 and AG037457 to S.I.; C.R.M. was a Glenn/AFAR Postdoctoral Fellow.

Competing interests

S.I. is a co-founder of Metro Midwest Biotech. N.E. de P., L.B.G., A.L.S., and D.R.S. filed PCT Application PCT/US15/22267, METHODS FOR TREATMENT OF VASCULAR ENDOTHELIAL DYSFUNCTION USING NICOTINAMIDE MONONUCLEOTIDE, on March 24, 2015. All other authors declare that they have no conflicts of interest.

HealthspanX observation

This paper is a key mechanistic basis for later human vascular studies, but its results remain preclinical.

Interpretive weight

Mechanistic context

Controlled aged-mouse study demonstrates vascular and oxidative-stress effects, but no human vascular outcome can be inferred.

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