Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106846 - 106846
Published: March 1, 2025
Language: Английский
npj Aging, Journal Year: 2025, Volume and Issue: 11(1)
Published: Jan. 27, 2025
Abstract Over the past five years, systemic NAD + (nicotinamide adenine dinucleotide) decline has been accepted to be a key driving force of aging in field research. The original version World concept was proposed 2009, providing an integrated view -centric, regulatory network for mammalian and longevity control. reformulated concept, 2.0, then 2016, emphasizing importance inter-tissue communications between hypothalamus peripheral tissues including adipose tissue skeletal muscle. There significant progress our understanding nicotinamide mononucleotide (NMN), intermediate, phosphoribosyltransferase (NAMPT), particularly extracellular NAMPT (eNAMPT). With these exciting developments, further 3.0, is now proposed, featuring multi-layered feedback loops mediated by NMN eNAMPT
Language: Английский
Citations
1
Neuroscience Research, Journal Year: 2023, Volume and Issue: 197, P. 18 - 24
Published: Jan. 17, 2023
The past 20 years of research on axon degeneration has revealed fine details how NAD biology controls axonal survival. Extensive data demonstrate that the precursor NMN binds to and activates pro-degenerative enzyme SARM1, so a failure convert sufficient into leads toxic accumulation degeneration. This involvement brings field an unexpected overlap with ageing extending healthy lifespan. A decline in levels throughout life, at least some tissues, is believed contribute age-related functional decay boosting production supplementation or other precursors gained attention as potential anti-ageing therapy. Recent have witnessed influx NMN-based products related molecules market, sold food supplements, many people taking these supplements daily. While several clinical trials are ongoing check safety profiles efficacy precursors, back their therapeutic use still lacking. Here, we discuss supplementation, SARM1 strategies, important question mind: considering can lead degeneration, this compatible its beneficial effect there circumstances which could become harmful?
Language: Английский
Citations
20
Aging and Disease, Journal Year: 2023, Volume and Issue: 15(2), P. 565 - 565
Published: Aug. 2, 2023
Nicotinamide adenine dinucleotide (NAD+) has recently attracted much attention due to its role in aging and lifespan extension. NAD+ directly indirectly affects many cellular processes, including metabolic pathways, DNA repair, immune cell activities. These mechanisms are critical for maintaining homeostasis. However, the decline levels with impairs tissue function, which been associated several age-related diseases. In fact, population steadily increasing worldwide, it is important restore reverse or delay these disorders. Therefore, there an demand healthy products that can mitigate aging, extend lifespan, halt consequences. this case, studies humans animals have targeted metabolism intermediates. Among them, nicotinamide mononucleotide (NMN), a precursor biosynthesis of NAD+, received from scientific community anti-aging properties. model organisms, ingestion NMN shown improve diseases probably death. Here, we review aspects mechanism absorption, as well potential NMN, recent preclinical clinical tests, adverse effects, limitations, perceived challenges.
Language: Английский
Citations
17
npj Aging, Journal Year: 2024, Volume and Issue: 10(1)
Published: Jan. 2, 2024
Abstract Nicotinamide adenine dinucleotide (NAD + ) is an essential metabolite for fundamental biological phenomena, including aging. mononucleotide (NMN) a key NAD intermediate that has been extensively tested as effective -boosting compound in mice and humans. However, the accurate measurement of NMN samples long challenge field. Here, we have established accurate, quantitative methodology measuring by using liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) with double isotopic standards. In this new methodology, matrix effects were properly adjusted, fate could be traced during sample processing. We demonstrated can accurately quantitate levels mouse plasma confirmed quick, direct uptake into blood circulation cells. This d ouble i sotope- me diated LC-MS/MS (dimeLC-MS/MS) easily expanded to other -related metabolites reliable standard biology.
Language: Английский
Citations
7
Endocrine Journal, Journal Year: 2024, Volume and Issue: 71(2), P. 153 - 169
Published: Jan. 1, 2024
Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator many biological processes, declines in multiple organs tissues with obesity. Administration an NAD+ intermediate, mononucleotide (NMN), replenishes intracellular mitigates aging- obesity-associated derangements animal models. In this human clinical study, we aimed to investigate safety effects 8-week oral administration NMN on biochemical, metabolic, ophthalmologic, sleep quality parameters as well chronological alterations content peripheral tissues. An 8-week, single-center, single-arm, open-label trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg capsules once daily before breakfast. The supplementation regimen well-tolerated; blood mononuclear cells increased over course administration. participants insulin oversecretion after glucose loading, modestly attenuated postprandial hyperinsulinemia, factor coronary artery disease (n = 3). conclusion, overall safely effectively boosted biosynthesis men, showing its potential alleviating hyperinsulinemia.
Language: Английский
Citations
7
Mechanisms of Ageing and Development, Journal Year: 2024, Volume and Issue: 218, P. 111917 - 111917
Published: Feb. 29, 2024
Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation NMN has been shown to improve blood NAD concentration. However, the optimal dose remains unclear. This post-hoc analysis double-blinded clinical trial involving 80 generally healthy adults aged 40 65 years. The participants received placebo or daily 300 mg, 600 900 mg for 60 days. Blood concentration, biological age, homeostatic model assessment insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline after supplement. A significant dose-dependent increase in concentration change (NADΔ) was observed following supplementation, large coefficient variation (29.2-113.3%) within group. NADΔ associated an improvement walking distance test SF-36 score. median effect score 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) 13.5 CI; 10.5-16.5 nmol/L), respectively. Because high interindividual variability monitoring can provide valuable insights tailoring personalized dosage regimens optimizing utilization.
Language: Английский
Citations
7
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: Aug. 30, 2024
Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into within the body after ingestion. NMN plays pivotal role several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. has emerged as key focus of research fields biomedicine, health care, food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights pathogenesis age- aging-related diseases. Given sustained global interest substantial market expectations for future, here, we comprehensively review milestones biotherapy over past 10 years. Additionally, highlight current field digestive system diseases, identifying existing problems challenges research. The overarching aim this is to provide references further exploration spectrum
Language: Английский
Citations
6
The Journals of Gerontology Series A, Journal Year: 2023, Volume and Issue: 78(12), P. 2435 - 2448
Published: April 17, 2023
Abstract Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance precursor compounds, such as riboside or mononucleotide, has profound effects on physiological function models of aging disease. Translation these compounds for oral supplementation humans been increasingly studied within the last 10 years; however, clinical evidence raising concentrations can improve is unclear. The goal this review was to synthesize published literature chronic precursors healthy age-related diseases. We identified riboside, co-administered pterostilbene, mononucleotide most common candidates investigations NAD+-boosting improving humans. Studies have performed generally midlife older adults, adults cardiometabolic risk factors overweight obesity, numerous patient populations. Supplementation safe, tolerable, increase related metabolites multiple tissues. Dosing regimens study durations vary greatly across interventions, small sample sizes limit data interpretation outcomes. Limitations future research directions suggested further our understanding potential efficacy extending human health span.
Language: Английский
Citations
15
Endocrine Reviews, Journal Year: 2023, Volume and Issue: 44(6), P. 1047 - 1073
Published: June 26, 2023
Abstract Recent research has unveiled an expansive role of NAD+ in cellular energy generation, redox reactions, and as a substrate or cosubstrate signaling pathways that regulate health span aging. This review provides critical appraisal the clinical pharmacology preclinical evidence for therapeutic effects precursors age-related conditions, with particular focus on cardiometabolic disorders, discusses gaps current knowledge. levels decrease throughout life; decline bioavailability been postulated to be contributor many diseases. Raising model organisms by administration improves glucose lipid metabolism; attenuates diet-induced weight gain, diabetes, diabetic kidney disease, hepatic steatosis; reduces endothelial dysfunction; protects heart from ischemic injury; left ventricular function models failure; cerebrovascular neurodegenerative disorders; increases span. Early human studies show can raised safely blood some tissues oral suggest benefit preventing nonmelanotic skin cancer, modestly reducing pressure improving profile older adults obesity overweight; injury at-risk patients; suppressing inflammation Parkinson disease SARS-CoV-2 infection. Clinical pharmacology, metabolism, mechanisms remain incompletely understood. We these early findings provide rationale adequately powered randomized trials evaluate efficacy augmentation strategy prevent treat metabolic disorders conditions.
Language: Английский
Citations
15
Molecules, Journal Year: 2023, Volume and Issue: 28(16), P. 6078 - 6078
Published: Aug. 15, 2023
Many studies have suggested that the oxidized form of nicotinamide adenine dinucleotide (NAD+) is involved in an extensive spectrum human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes. Further, healthy aging longevity appear to be closely related NAD+ its metabolites, riboside (NR) mononucleotide (NMN). As a dietary supplement, NR appears well tolerated, having better pharmacodynamics greater potency. Unfortunately, reactive molecule, often unstable during manufacturing, transport, storage. Recently, work prebiotic chemistry discovered borate considerably more stable than itself. However, immediately upon consumption, dissociates from lost body through dilution binding other species, notably carbohydrates such as fructose glucose. The left behind expected behave pharmacologically ways identical This review provides comprehensive summary (through Q1 2023) literature makes case for consumption supplement. It then summarizes challenges delivering quality consumers using standard synthesis, manufacture, shipping, storage approaches. concludes by outlining advantages these processes.
Language: Английский
Citations
14