Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Igarashi, Masaki; Nakagawa-Nagahama, Yoshiko; Miura, Masaomi; Kashiwabara, Kosuke; Yaku, Keisuke; Sawada, Mikio; Sekine, Rika; Fukamizu, Yuichiro; Sato, Toshiya; Sakurai, Takanobu; Sato, Jiro; Ino, Kenji; Kubota, Naoto; Nakagawa, Takashi; Kadowaki, Takashi; Yamauchi, Toshimasa

doi:10.1038/s41514-022-00084-z

Cited by 50 publications

(57 citation statements)

References 48 publications

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“…Supplementation with NMN increases muscle insulin sensitivity, insulin signaling, and muscle remodeling in prediabetic women. 382 NMN prevents aging-related muscle dysfunctions 383 and shows benefits in improving aerobic capacity, cardiovascular fitness, sleep quality, fatigue, and physical performance. 89 , 384 As for NR, clinical trials indicate that NR suppresses inflammatory activation of PBMCs in heart failure patients 385 and decreases the levels of inflammatory cytokines in the serum and cerebrospinal fluid of Parkinson’s disease (PD) patients.…”

Section: Epigenetic Regulation Of Agingmentioning

confidence: 99%

Epigenetic regulation of aging: implications for interventions of aging and diseases

Wang

Liu

et al. 2022

Sig Transduct Target Ther

194

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Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks, including genetic and epigenetic alterations. These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, and RNA modification, all of which participate in the regulation of the aging process, and hence contribute to aging-related diseases. Therefore, understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging. Indeed, aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models. Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, and calibrating circadian rhythm, has been demonstrated to delay aging. Furthermore, various clinical trials for aging intervention are ongoing, providing more evidence of the safety and efficacy of these therapies. Here, we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases. A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.

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Section: Epigenetic Regulation Of Agingmentioning

confidence: 99%

Epigenetic regulation of aging: implications for interventions of aging and diseases

Wang

Liu

et al. 2022

Sig Transduct Target Ther

194

View full text Add to dashboard Cite

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“…A similar RCT reported that oral 300 mg/day NMN supplement was safe and significantly improved several blood biomarkers, such as HbA1c and HDL-C, but has significantly reduced blood NAD level for the 17 postmenopausal female participants after an 8-week trial [ 12 ]. A 12-week RCT with a fixed 250 mg/day oral NMN dose on 42 healthy older men showed that blood NAD concentration was significantly elevated and NMN was well tolerated, but NMN supplementation produced mixed results on skeletal muscle strength tests [ 13 ]. A separate RCT disclosed that, after intervention also with a fixed 250 mg/day NMN oral dose for 12 weeks on 30 healthy males and females, blood NAD concentration increased significantly starting at week 4 until the end of treatment at week 12 and returned to original level 4 weeks after NMN treatment, and the NMN supplementation was safe and well tolerated [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Yi¹,

Maier

Tao

et al. 2022

GeroScience

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In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421.

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“…We initially employed the MTS assay to measure the cytotoxicity of PM-conditioned medium (PCM) from PM-exposed KU812 cells, NMN or Q10, on HDFs. HDFs were treated with PCM for 8 h followed by 1 μM NMN or 100 nM Q10 for 16 h. The concentrations of NMN and Q10 use were based on previously reported studies [ 29 , 30 ]. Cell viability was expressed as a percentage compared to the control, which was treated with a supernatant collected from DMSO-stimulated KU812 cells.…”

Section: Resultsmentioning

confidence: 99%

Nicotinamide Mononucleotide and Coenzyme Q10 Protects Fibroblast Senescence Induced by Particulate Matter Preconditioned Mast Cells

Chang

Yang

Huang

2022

IJMS

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Particulate matter (PM) pollutants impose a certain degree of destruction and toxicity to the skin. Mast cells in the skin dermis could be activated by PMs that diffuse across the blood vessel after being inhaled. Mast cell degranulation in the dermis provides a kind of inflammatory insult to local fibroblasts. In this study, we evaluated human dermal fibroblast responses to conditioned medium from KU812 cells primed with PM. We found that PM promoted the production of proinflammatory cytokines in mast cells and that the cell secretome induced reactive oxygen species and mitochondrial reactive oxygen species production in dermal fibroblasts. Nicotinamide mononucleotide or coenzyme Q10 alleviated the generation of excessive ROS and mitochondrial ROS induced by the conditioned medium from PM-activated KU812 cells. PM-conditioned medium treatment increased the NF-κB expression in dermal fibroblasts, whereas NMN or Q10 inhibited p65 upregulation by PM. The reduced sirtuin 1 (SIRT 1) and nuclear factor erythroid 2-related Factor 2 (Nrf2) expression induced by PM-conditioned medium was reversed by NMN or Q10 in HDFs. Moreover, NMN or Q10 attenuated the expression of senescent β-galactosidase induced by PM-conditioned KU812 cell medium. These findings suggest that NMN or Q10 ameliorates PM-induced inflammation by improving the cellular oxidative status, suppressing proinflammatory NF-κB, and promoting the levels of the antioxidant and anti-inflammatory regulators Nrf2 and SIRT1 in HDFs. The present observations help to understand the factors that affect HDFs in the dermal microenvironment and the therapeutic role of NMN and Q10 as suppressors of skin aging.

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Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men

Cited by 50 publications

References 48 publications

Epigenetic regulation of aging: implications for interventions of aging and diseases

Epigenetic regulation of aging: implications for interventions of aging and diseases

The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial

Nicotinamide Mononucleotide and Coenzyme Q10 Protects Fibroblast Senescence Induced by Particulate Matter Preconditioned Mast Cells

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