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Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
Open accessAbstract
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.
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In the citing paper
“Recently, treatment with nicotinamide mononucleotide, which enhances NAD + production, has been shown to improve mitochondrial respiration and to prevent aging-associated gene expression changes in muscles of mice and humans92.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [92]
In the citing paper
“long-term (1-year) feeding of mice with NMN starting at 5 months of age increased whole-body insulin sensitivity, energy metabolism and physical activity and improved lipid profiles with no obvious toxic effects199.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [199]
In the citing paper
“These studies also documented that NMN has a significant effect on improving disease conditions and reducing age-related physiological decline [203–206].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [205]
In the citing paper
“Previous studies have demonstrated that NMN can effectively alleviate age-related physiological decline in wild-type mice fed with conventional feed [205]”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [205]
In the citing paper
“many of these phenotypes are regulated by NAD+ availability and the activity of NAD+-dependent enzymes”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Mills et al., 2016
In the citing paper
“Recently, several reports have demonstrated that increasing NAD+ levels in tissues, through the use of NAD+ precursors such as NMN and NR, improves health span, mitigates age and metabolic disease-associated decline, and may increase longevity”
From A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD+ Decline (2018) · cites this paper as Mills et al., 2016
In the citing paper
“In 22-month-old mice, NMN restored NAD+ levels and markers of mitochondrial decline during ageing48, while reducing age-associated body weight gain and increasing energy metabolism and physical activity254.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [254]
In the citing paper
“Nicotinamide mononucleotide administration to mice also enhances energy metabolism, promotes physical activity, improves lipid profiles, and ameliorates age-related pathophysiology (267).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [267]
In the citing paper
“Long-term administration of nicotinamide mononucleotide enhances age-associated C57BL/6N mice locomotor activity and enhances mitochondrial respiratory capacity in skeletal muscle [70].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [70]
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Metadata
- Authors
- Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., Yoshino, J., & Imai, S.-I.
- Affiliations
- Washington University in St. Louis (US)
- Oriental Yeast Co., Ltd. (Japan) (JP)
- Queen's University Belfast (GB)
- Corresponding author
- Yoshino, Jun
- Imai, Shin-ichiro
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 24
- Issue
- 6
- Pages
- 795-806
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5668137
- OpenAlex
- W2546015443
- Cited by
- 930
- References
- 45
- Citations by year
- 2026: 127 · 2025: 134 · 2024: 127 · 2023: 96 · 2022: 106 · 2021: 111 · 2020: 74 · 2019: 63 · 2018: 58 · 2017: 31 · 2016: 1
- FWCI
- 29.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Diabetes Research Center (P30 DK020579)
- Nutrition Obesity Research Center (P30 DK56341)
- Research to Prevent Blindness Physician Scientist Award
- Research to Prevent Blindness Unrestricted Grant to Department of Ophthalmology
- Hope Center for Neurological Disorders
- Biotechnology and Biological Science Research Council (BBSRC; BB/N001842/1)
- Washington University
- Oriental Yeast Co.
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- nicotinamide mononucleotide, NAD biosynthesis, aging, anti-aging interventions, energy metabolism, insulin sensitivity, plasma lipid profile, weight gain, physical activity, eye function, mitochondrial oxidative metabolism, skeletal muscle
- MeSH terms
- Administration, Oral, Aging, Animals, Darkness, Drinking, Eating, Energy Metabolism, Food, Gene Expression Regulation, Insulin, Lipids, Lymphocytes, Male, Mice, Inbred C57BL, Mitochondria, NAD, Nicotinamide Mononucleotide, Physical Conditioning, Animal, Time Factors, Weight Gain, Bone Density, Muscle, Skeletal, Cell Respiration, Myeloid Cells
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