NAD+ metabolism and its roles in cellular processes during ageing

Nature Reviews Molecular Cell Biology, Год журнала: 2020, Номер 22(2), С. 119 - 141

Опубликована: Дек. 22, 2020

Язык: Английский

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CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Ноя. 30, 2020

CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or receptor adhesive functions. be found expressed either on the cell surface, where it may face extracellular milieu cytosol, in compartments, such endoplasmic reticulum, nuclear membrane, mitochondria. The main expression of observed hematopoietic cells, some cell-type specific differences between mouse human. role immune cells ranges from modulating differentiation to effector functions during inflammation, regulate recruitment, cytokine release, NAD availability. In line appears also play critical inflammatory processes autoimmunity, although whether has pathogenic regulatory effects varies depending disease, cell, animal model analyzed. Given complexity physiology been difficult completely understand biology this autoimmune inflammation. review, we analyze current knowledge controversies regarding inflammation autoimmunity novel molecular tools clarify gaps field.

Язык: Английский

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Role of NAD+ in regulating cellular and metabolic signaling pathways

Molecular Metabolism, Год журнала: 2021, Номер 49, С. 101195 - 101195

Опубликована: Фев. 18, 2021

Nicotinamide adenine dinucleotide (NAD+), a critical coenzyme present in every living cell, is involved myriad of metabolic processes associated with cellular bioenergetics. For this reason, NAD+ often studied the context aging, cancer, and neurodegenerative disorders. Cellular depletion compromised adaptive stress responses, impaired neuronal plasticity, DNA repair, senescence. Increasing evidence has shown efficacy boosting levels using precursors various diseases. This review provides comprehensive understanding into role aging other pathologies discusses potential therapeutic targets. An alteration NAD+/NADH ratio or pool size can lead to derailment biological system contribute disorders, tumorigenesis. Due varied distribution different locations within cells, direct NAD+-dependent humans remains unestablished. In regard, longitudinal studies are needed quantify its related metabolites. Future research should focus on measuring fluxes through pathways synthesis degradation.

Язык: Английский

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Kynurenine pathway, NAD+ synthesis, and mitochondrial function: Targeting tryptophan metabolism to promote longevity and healthspan

Experimental Gerontology, Год журнала: 2020, Номер 132, С. 110841 - 110841

Опубликована: Янв. 16, 2020

Язык: Английский

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NAD ⁺ homeostasis in human health and disease

EMBO Molecular Medicine, Год журнала: 2021, Номер 13(7)

Опубликована: Май 27, 2021

Язык: Английский

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Nicotinamide mononucleotide (NMN) as an anti-aging health product – Promises and safety concerns

Journal of Advanced Research, Год журнала: 2021, Номер 37, С. 267 - 278

Опубликована: Авг. 11, 2021

Elderly population has been progressively rising in the world, thus demand for anti-aging heath products to assure longevity as well ameliorate age-related complications is also on rise. Among various health products, nicotinamide mononucleotide (NMN) gaining attentions of consumers and scientific community.This article intends provide an overview current knowledge promises safety concerns NMN product.Nicotinamide adenine dinucleotide (NAD+) levels body deplete with aging it associated downregulation energy production mitochondria, oxidative stress, DNA damage, cognitive impairment inflammatory conditions. However, NMN, precursor NAD+, can slow down this process by elevating NAD+ body. A number vivo studies have indicated affirmative results therapeutic effects age-induced supplementation. One preclinical one clinical study conducted investigate administration while a few more human trials are being conducted. As there large influx based market, proper investigations urgently needed find out effectiveness

Язык: Английский

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SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways

Scientific Reports, Год журнала: 2021, Номер 11(1)

Опубликована: Апрель 14, 2021

Abstract The NAD + -dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote function such as overexpression or boosters alleviate complications. We previously reported SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, dysregulated metabolism. Here, we characterized SIRT1-depleted adipocytes quantitative mass spectrometry-based proteomics, gene-expression biochemical analyses, mitochondrial studies. found promoted biogenesis respiration expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, thyroid responsive protein was SIRT1-dependent. Independent validation the proteomics dataset uncovered SIRT1-dependence SREBF1c PPARα signaling adipocytes. nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) during differentiation constitutively repressed NMNAT1 3 levels. Supplementing with booster (NMN) increased levels SIRT1, PGC-1α its transcriptional targets, reduced pro-fibrotic collagens (Col6A1 Col6A3) a SIRT1-dependent manner. Investigating impact functional interaction insights into how metabolism modulates could potentially lead new avenues developing therapeutics for obesity

Язык: Английский

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Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment

Hepatology Communications, Год журнала: 2024, Номер 8(7)

Опубликована: Июль 1, 2024

With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events MASLD. Recent studies have highlighted cross-talk between microbiota mitochondria, mitochondria recognized pivotal targets of to modulate host's physiological state. plays role associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, fibrosis. Metabolites crucial mediators that influence extraintestinal organs. Additionally, regulation composition may serve promising therapeutic strategy for This study reviewed potential roles several common metabolites MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss current treatments probiotics, prebiotics, antibiotics, fecal transplantation. These methods concentrate restoring promote host health.

Язык: Английский

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Nicotinamide Mononucleotide: A Promising Molecule for Therapy of Diverse Diseases by Targeting NAD+ Metabolism

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Апрель 28, 2020

NAD+, a co-enzyme involved in great deal of biochemical reactions, has been found to be network node diverse biological processes. In mammalian cells, NAD+ is synthetized, predominantly through NMN, replenish the consumption by NADase participating physiologic processes including DNA repair, metabolism and cell death. Correspondingly, aberrant observed many diseases. this review, we discuss how homeostasis maintained healthy condition provide several age-related pathological examples related with unbalance. The sirtuins family, whose functions are NAD-dependent also reviewed. Administration NMN surprisingly demonstrated amelioration conditions some disease mouse models. Further clinical trials have launched investigate safety benefits NMN. production pathways essential for more precise understanding therapy such as diabetes, ischemia-reperfusion injury, heart failure, Alzheimer's retinal degeneration.

Язык: Английский

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Mechanism of action of Imeglimin: A novel therapeutic agent for type 2 diabetes

Diabetes Obesity and Metabolism, Год журнала: 2020, Номер 23(3), С. 664 - 673

Опубликована: Дек. 3, 2020

Imeglimin is an investigational first-in-class novel oral agent for the treatment of type 2 diabetes (T2D). Several pivotal phase III trials have been completed with evidence statistically significant glucose lowering and a generally favourable safety tolerability profile, including lack severe hypoglycaemia. Imeglimin's mechanism action involves dual effects: (a) amplification glucose-stimulated insulin secretion (GSIS) preservation β-cell mass; (b) enhanced action, potential inhibition hepatic output improvement in signalling both liver skeletal muscle. At cellular molecular level, underlying may involve correction mitochondrial dysfunction, common element T2D pathogenesis. It has observed to rebalance respiratory chain activity (partial Complex I deficient activity), resulting reduced reactive oxygen species formation (decreasing oxidative stress) prevention permeability transition pore opening (implicated preventing cell death). In islets derived from diseased rodents T2D, also enhances ATP generation induces synthesis nicotinamide adenine dinucleotide (NAD+ ) via 'salvage pathway'. addition playing key role as co-factor, NAD+ metabolites contribute increase GSIS (via Ca++ mobilization). shown preserve mass T2D. Overall, appears target root cause T2D: defective energy metabolism. This mode unique differ that other major therapeutic classes, biguanides, sulphonylureas glucagon-like peptide-1 receptor agonists.

Язык: Английский

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