Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice
By K. Mills, Shohei Yoshida, L. Stein, Alessia Grozio, Shunsuke Kubota, Y. Sasaki, P. Redpath, M. Migaud, R. Apte, K. Uchida and 2 more. Cell Metabolism, 2016
803 citations recorded by the source corpus.
Summary 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.
Subfields: Geriatrics and Gerontology, Oncology, Physiology
View Paper: https://www.semanticscholar.org/paper/2b5f09a280fd6f4a5087a20e7e05381716765979
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Citations in the corpus
- Mechanisms of Vascular Aging (2018, background): “sirtuin-mediated pathways and reversing age-related decline in mitochondrial function.(71) Other potential mechanisms con-”
- NAD+ intermediates: The biology and therapeutic potential of NMN and NR (2017, positive): “…the fact that intraperitoneal or oral administration of NMN (300–500 mg/kg) immediately (within 5 min) increases NMN in plasma and then NAD+ content in peripheral organs (Mills et al., 2016; Yoshino et al., 2011), suggesting the presence of an active NMN uptake system in the gut and other organs.”
- NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential (2020, background): “Moreover, NMN administration can significantly elevate NAD biosynthesis in white adipose tissue, heart and the liver, but not the NAD content in brown adipose tissue and kidney, suggesting a tissue- and cell-type-specific transportation of NMN to cells or tissues for NAD biosynthesis presumably due ”