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Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.
Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael.
Affiliation
  • Mitchell SJ; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Bernier M; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Aon MA; 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.
  • Cortassa S; Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Kim EY; 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.
  • Fang EF; Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Palacios HH; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Ali A; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Navas-Enamorado I; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Di Francesco A; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Kaiser TA; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Waltz TB; Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Zhang N; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
  • Ellis JL; Sirtris, a GSK Company, 200 Technology Square, Cambridge, MA 02139, USA.
  • Elliott PJ; Sirtris, a GSK Company, 200 Technology Square, Cambridge, MA 02139, USA.
  • Frederick DW; Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Bohr VA; Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Schmidt MS; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
  • Brenner C; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
  • Sinclair DA; Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA.
  • Sauve AA; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
  • Baur JA; Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • de Cabo R; Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA. Electronic address: decabora@grc.nia.nih.gov.
Cell Metab ; 27(3): 667-676.e4, 2018 03 06.
Article in En | MEDLINE | ID: mdl-29514072
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Niacinamide / Dietary Supplements / Healthy Aging / Liver / NAD Limits: Animals Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2018 Document type: Article Affiliation country: United States Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Niacinamide / Dietary Supplements / Healthy Aging / Liver / NAD Limits: Animals Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2018 Document type: Article Affiliation country: United States Country of publication: United States