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Cell Metab. 2018 Mar 6;27(3):667-676.e4. doi: 10.1016/j.cmet.2018.02.001.

Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.

Author information

1
Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
2
Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA; Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
3
Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
4
Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA; Functional Genomics Research Center, KRIBB, Daejeon 305-806, Republic of Korea.
5
Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
6
Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
7
Sirtris, a GSK Company, 200 Technology Square, Cambridge, MA 02139, USA.
8
Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
10
Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.
11
Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Electronic address: decabora@grc.nia.nih.gov.

Abstract

The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+, is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD+ nor NADP+ was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.

KEYWORDS:

NAD; NAMPT; aging; calorie restriction mimetics; dietary interventions; geroscience; high-fat diet; nicotinamide; sirtuin

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