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

GeroScience, Journal Year: 2022, Volume and Issue: 45(1), P. 29 - 43

Published: Dec. 8, 2022

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

Language: Английский

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Cellular senescence, DNA damage, and neuroinflammation in the aging brain

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(6), P. 461 - 474

Published: May 9, 2024

Language: Английский

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The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update

Advances in Nutrition, Journal Year: 2023, Volume and Issue: 14(6), P. 1416 - 1435

Published: Aug. 23, 2023

The importance of nicotinamide adenine dinucleotide (NAD+) in human physiology is well recognized. As the NAD+ concentration skin, blood, liver, muscle and brain are thought to decrease with age, finding ways increase status could possibly influence ageing process associated metabolic sequelae. Nicotinamide mononucleotide (NMN) a precursor for biosynthesis, vitro/in vivo studies have demonstrated that NMN supplementation increases mitigate ageing-related disorders such as oxidative stress, DNA damage, neurodegeneration inflammatory responses. promotion an anti-ageing health supplement has gained popularity due findings; however, since most evaluating effects been conducted cell or animal models, concern remains regarding safety physiological population. Nonetheless, dozen clinical trials currently underway. This review summarizes current progress these NMN/NAD+ biology clarify potential shed light on future study directions.

Language: Английский

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NAD metabolism: Role in senescence regulation and aging

Aging Cell, Journal Year: 2023, Volume and Issue: 23(1)

Published: July 9, 2023

Abstract The geroscience hypothesis proposes that addressing the biology of aging could directly prevent onset or mitigate severity multiple chronic diseases. Understanding interplay between key aspects biological hallmarks is essential in delivering promises hypothesis. Notably, nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several aging, including cellular senescence, and changes NAD metabolism have been shown to be involved process. relationship senescence appears complex. On one hand, accumulation DNA damage mitochondrial dysfunction induced by low + can promote development senescence. other state occurs during may inhibit SASP as this secretory phenotype are both highly metabolically demanding. However, date, impact on progression has not fully characterized. Therefore, explore implications replacement therapies, it consider their interactions We propose a comprehensive understanding boosting strategies senolytic agents necessary advance field.

Language: Английский

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Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Feb. 16, 2023

Abstract Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD + ) precursor mononucleotide (NMN) prevents reduction NAD levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports NMN supplementation humans. Thus, this study aimed to investigate influence a 12-week on biochemical metabolic health parameters. A randomized, double-blind, placebo-controlled, parallel-group trial was conducted. total 36 healthy middle-aged participants received one capsule either 125 mg or placebo twice day. Among metabolites, serum were significantly higher intake group than group. Pulse wave velocity values indicating arterial stiffness tended decrease no significant difference found between two groups. Long-term at 250 mg/day well tolerated did not cause adverse events. safely effectively elevated metabolism adults. Additionally, showed potential alleviating stiffness.

Language: Английский

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The therapeutic perspective of NAD+ precursors in age-related diseases

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 702, P. 149590 - 149590

Published: Feb. 2, 2024

Nicotinamide adenine dinucleotide (NAD

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Regulation of and challenges in targeting NAD+ metabolism

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(10), P. 822 - 840

Published: July 18, 2024

Language: Английский

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Sirtuins in kidney diseases: potential mechanism and therapeutic targets

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Sirtuins, which are NAD + -dependent class III histone deacetylases, involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins essential regulators of cellular function organismal health. Increasing evidence suggests that the development age-related diseases, kidney is associated with aberrant expression sirtuins, regulation sirtuins activity can effectively improve delay progression disease. In this review, we summarise current studies highlighting role renal diseases. First, discuss sirtuin family members their main mechanisms action. We then outline possible roles cell types Finally, compounds activate or inhibit consequently ameliorate conclusion, targeted modulation a potential therapeutic strategy for

Language: Английский

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A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(4)

Published: Feb. 14, 2024

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 have been identified humans with congenital malformations defined as deficiency disorder (CNDD). Here, we 13 further individuals predicted to be damaging, phenotypes ranging from multiple severe complete absence malformation. Enzymatic assessment variant deleteriousness vitro revealed protein domain-specific perturbation, complemented by structure modeling silico. We reproduced NADSYN1-dependent CNDD mice assessed various maternal precursor supplementation strategies prevent adverse pregnancy outcomes. While Nadsyn1+/- mothers, any B3 vitamer was suitable raise NAD, preventing embryo loss malformation, Nadsyn1-/- mothers required amidated precursors (nicotinamide or nicotinamide mononucleotide) bypassing their metabolic block. The circulatory metabolome before after a consistent signature utility patient identification. Our data collectively improve clinical diagnostics CNDD, provide guidance therapeutic prevention suggest an ongoing need maintain levels via birth.

Language: Английский

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Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma

Molecular Carcinogenesis, Journal Year: 2024, Volume and Issue: 63(4), P. 577 - 588

Published: Jan. 10, 2024

Abstract Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. cells were treated with NMN (125, 250, and 500 μM), then adenine dinucleotide (NAD + ) NADH levels measured to calculate NAD /NADH ratio. Cell proliferation, apoptosis, autophagy ferroptosis determined. AMPK was knocked down confirm involvement AMPK/mTOR signaling. Furthermore, tumor‐inhibitory effect xenograft models. Exposure dose‐dependently increased level ratio cells. After treatment, cell proliferation inhibited, whereas apoptosis enhanced both lines. Additionally, autophagy/ferroptosis activated pathway knockdown partially rescued effects vitro. treatment restrained tumor growth nude mice, autophagy/ferroptosis, promoted necrosis tissues. The results indicate that inhibits progression by inducing via may serve as promising agent for treatment.

Language: Английский

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