NAD+ metabolism, stemness, the immune response, and cancer

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Янв. 1, 2021

NAD+ was discovered during yeast fermentation, and since its discovery, important roles in redox metabolism, aging, longevity, the immune system DNA repair have been highlighted. A deregulation of levels has associated with metabolic diseases aging-related diseases, including neurodegeneration, defective responses, cancer. acts as a cofactor through interplay NADH, playing an essential role many enzymatic reactions energy such glycolysis, oxidative phosphorylation, fatty acid oxidation, TCA cycle. also plays deacetylation by sirtuins ADP ribosylation damage/repair PARP proteins. Finally, different NAD hydrolase proteins consume while converting it into ADP-ribose or cyclic counterpart. Some these proteins, CD38, seem to be extensively involved response. Since cannot taken directly from food, metabolism is essential, NAMPT key enzyme recovering nicotinamide generating most cellular pools. Because complex network pathways which enzyme, NAMPT, cancer understandable. In present work, we review ways that they may influence system, stemness, some ongoing research on therapeutic approaches.

Язык: Английский

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

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Ноя. 7, 2022

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

Язык: Английский

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Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

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

Опубликована: Март 26, 2020

Mitochondrial dysfunction constitutes one of the hallmarks aging and is characterized by irregular mitochondrial morphology, insufficient ATP production, accumulation DNA (mtDNA) mutations, increased production reactive oxygen species (ROS) consequent oxidative damage to nucleic acids, proteins lipids. Mitophagy, a quality control mechanism enabling degradation damaged superfluous mitochondria, prevents such detrimental effects reinstates cellular homeostasis in response stress. To date, there increasing evidence that mitophagy significantly impaired several human pathologies including age-related diseases as neurodegenerative disorders, cardiovascular cancer. Therapeutic interventions aiming at induction may have potency ameliorate these dysfunctions. In this review, we summarize recent findings on mechanisms controlling its role development pathologies.

Язык: Английский

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The Warburg Effect 97 Years after Its Discovery

Cancers, Год журнала: 2020, Номер 12(10), С. 2819 - 2819

Опубликована: Сен. 30, 2020

The deregulation of the oxidative metabolism in cancer, as shown by increased aerobic glycolysis and impaired phosphorylation (Warburg effect), is coordinated genetic changes leading to activation oncogenes loss oncosuppressor genes. understanding metabolic cancer cells necessary prevent cure cancer. In this review, we illustrate comment principal molecular variations cells, involved their anomalous behavior, that include modifications metabolism, promote a decrease oxygen consumption susceptibility correlations defective mitochondria, relationships between Warburg effect tumor therapy, recent studies reevaluate effect. Taken together, these observations indicate an epiphenomenon transformation process essential for development malignancy.

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 Metabolism in Cancer Therapeutics

Frontiers in Oncology, Год журнала: 2018, Номер 8

Опубликована: Дек. 12, 2018

Cancer cells have a unique energy metabolism for sustaining rapid proliferation. The preference anaerobic glycolysis under normal oxygen conditions is trait of cancer and designated as the Warburg effect. Enhanced also supports generation nucleotides, amino acids, lipids, folic acid building blocks cell division. Nicotinamide adenine dinucleotide (NAD) co-enzyme that mediates redox reactions in number metabolic pathways, including glycolysis. Increased NAD levels enhance fuel cells. In fact, nicotinamide phosphoribosyltransferase (Nampt), rate-limiting enzyme synthesis mammalian cells, frequently amplified several addition, Nampt-specific inhibitors significantly deplete subsequently suppress proliferation through inhibition production such glycolysis, tricarboxylic (TCA) cycle, oxidative phosphorylation. serves substrate poly(ADP-ribose) polymerase (PARP), sirtuin, gylycohydrolase (CD38 CD157); thus, regulates DNA repair, gene expression, stress response these enzymes. Thus, implicated pathogenesis beyond considered promising therapeutic target treatment. this review, we present recent findings with respect to pathogenesis. We discuss current future perspectives regarding therapeutics pathways.

Язык: Английский

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Implications of altered NAD metabolism in metabolic disorders

Journal of Biomedical Science, Год журнала: 2019, Номер 26(1)

Опубликована: Май 11, 2019

Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that participates in various energy metabolism pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Besides, it a required cofactor for post-translational modifications such as ADP-ribosylation deacetylation by poly (ADP-ribose) polymerases (PARPs) sirtuins, respectively. Thus, NAD regulates metabolism, DNA damage repair, gene expression, stress response through these enzymes. Numerous studies have shown levels decrease with aging under disturbed nutrient conditions, obesity. Additionally, decline closely related to the development of metabolic disorders, diabetes fatty liver disease. In addition, many revealed administration precursors, nicotinamide mononucleotide (NMN) riboside (NR), efficiently increase tissues prevent diseases. These precursors are contained natural foods, cow milk, vegetables, meats. Therefore, altered can be practical target nutritional intervention. Recently, several human clinical trials using been conducted investigate safety, pharmacokinetics, efficacy against disorders glucose intolerance. this review, we summarize current knowledge on implications diseases discuss outcomes recent trials.

Язык: Английский

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NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Март 19, 2020

Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate (NAPRT) are two intracellular enzymes that catalyze the first step in biosynthesis of NAD from nicotinamide nicotinic acid, respectively. By fine tuning levels, they involved regulation/reprogramming cellular metabolism control activity NAD-dependent enzymes, including sirtuins, PARPs NADases. However, during evolution both acquired novel functions as extracellular endogenous mediators inflammation. It is well known stress and/or damage induce release milieu molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune through binding pattern recognition receptors (PRRs), such Toll-like (TLRs), activate inflammatory responses. Increasing evidence suggests (e)NAMPT eNAPRT soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported several metabolic disorders, obesity, diabetes cancer, while emerging a biomarker sepsis septic shock. This review will discuss available data concerning dual role this unique family enzymes.

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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The role of cellular senescence in female reproductive aging and the potential for senotherapeutic interventions

Human Reproduction Update, Год журнала: 2021, Номер 28(2), С. 172 - 189

Опубликована: Ноя. 11, 2021

Advanced maternal age is associated with decreased oocyte quantity and quality as well uterine placental dysfunctions. These changes lead to infertility, pregnancy complications birth defects in the offspring. As mean of giving increasing worldwide, prevention age-associated infertility complications, along more frequent use ART, become extremely important. Currently, significant research being conducted unravel mechanisms underlying female reproductive aging. Among potential involved, recent evidence has suggested a contributing role for cellular senescence, state irreversible growth arrest characterized by hypersecretory pro-inflammatory phenotype. Elucidating senescence aging holds developing novel less invasive therapeutic measures prevent or even reverse increase offspring wellbeing.

Язык: Английский

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