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.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: Mills
authors.affiliation: Oriental Yeast Company, Tokyo 174-0051, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Liana R
authors.initials: LR
authors.lastname: Stein
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Grozio
authors.affiliation: Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yo
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT7 1NN, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Redpath
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland BT7 1NN, UK.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Migaud
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Ophthalmology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Rajendra S
authors.initials: RS
authors.lastname: Apte
authors.affiliation: Oriental Yeast Company, Tokyo 174-0051, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Division of Geriatrics and Nutritional Science, Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: jyoshino@wustl.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: imaishin@wustl.edu.
authors.forename: Shin-Ichiro
authors.initials: SI
authors.lastname: Imai
mesh_terms: D000284:Administration, Oral; D000375:Aging / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D003624:Darkness; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005502:Food; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008055:Lipids / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009537:Nicotinamide Mononucleotide / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D010805:Physical Conditioning, Animal; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D007328:Insulin; D008055:Lipids; D009243:NAD; D009537:Nicotinamide Mononucleotide
keywords: NAD(+); NAD(+) precursor; NMN; aging; anti-aging; energy metabolism; eye function; glucose metabolism; insulin sensitivity; mitochondria; nicotinamide mononucleotide