@article{a9199a4d99774a498a390d527f47693b,
title = "Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice",
abstract = "NAD+ availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12-month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD+ in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice. Without any obvious toxicity or deleterious effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies. Consistent with these phenotypes, NMN prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle. These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans.",
keywords = "NAD, NAD precursor, NMN, aging, anti-aging, energy metabolism, eye function, glucose metabolism, insulin sensitivity, mitochondria, nicotinamide mononucleotide",
author = "Mills, {Kathryn F.} and Shohei Yoshida and Stein, {Liana R.} and Alessia Grozio and Shunsuke Kubota and Yo Sasaki and Philip Redpath and Migaud, {Marie E.} and Apte, {Rajendra S.} and Koji Uchida and Jun Yoshino and Imai, {Shin ichiro}",
note = "Funding Information: We thank Sunnie Hsiung, Megan Hurt-Arb, and Terri Pietka for their technical assistance. We also thank late Toshikuni Naito, Ryuji Nakamura, Masashi Nakagawa, Hideo Arai, Ken Kanzaki, Hisataka Yasuda, and Yoshifumi Masuda in Oriental Yeast Co. for their support to this sponsored research project, Kazuo Tsubota and Takaaki Inaba at Keio University School of Medicine for their technical support for tear production measurement, Mr. Tsunemaru Tanaka and Ms. Megumi Tanaka for their generous gift of NMN, members of the S.I. lab for critical comments and suggestions on this study, and staff members in the core facilities provided by the Diabetes Research Center ( P30 DK020579 ), Nutrition Obesity Research Center ( P30 DK56341 ), a Research to Prevent Blindness Physician Scientist Award (R.S.A.) and a Research to Prevent Blindness Unrestricted Grant to Department of Ophthalmology , and the Hope Center for Neurological Disorders at Washington University. M.E.M. is supported by the Biotechnology and Biological Science Research Council ( BBSRC; BB/N001842/1 ). This work was conducted thoroughly under a sponsored research agreement between Washington University and Oriental Yeast Co. R.S.A. is a co-founder of Metro Midwest Biotech, and M.E.M. serves as a consultant for ChromaDex. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = dec,
day = "13",
doi = "10.1016/j.cmet.2016.09.013",
language = "English",
volume = "24",
pages = "795--806",
journal = "Cell metabolism",
issn = "1550-4131",
number = "6",
}