NAD ⁺ Metabolism in Cardiac Health, Aging, and Disease

Circulation, Год журнала: 2021, Номер 144(22), С. 1795 - 1817

Опубликована: Ноя. 29, 2021

Nicotinamide adenine dinucleotide (NAD + ) is a central metabolite involved in energy and redox homeostasis as well DNA repair protein deacetylation reactions. Pharmacological or genetic inhibition of NAD -degrading enzymes, external supplementation precursors, transgenic overexpression -generating enzymes have wide positive effects on metabolic health age-associated diseases. pools tend to decline with normal aging, obesity, hypertension, which are all major risk factors for cardiovascular disease, replenishment extends healthspan, avoids syndrome, reduces blood pressure preclinical models. In addition, experimental elevation improves atherosclerosis, ischemic, diabetic, arrhythmogenic, hypertrophic, dilated cardiomyopathies, different modalities heart failure. Here, we critically discuss cardiomyocyte-specific circuitries metabolism, comparatively evaluate distinct precursors their efficacy, raise outstanding questions the optimal design clinical trials supraphysiological elevations assessed prevention treatment cardiac We surmise that patients hitherto intractable diseases such failure preserved ejection fraction may profit from administration precursors. The development -centered treatments will rely technological conceptual progress fine regulation metabolism.

Язык: Английский

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Nutrients to Improve Mitochondrial Function to Reduce Brain Energy Deficit and Oxidative Stress in Migraine

Nutrients, Год журнала: 2021, Номер 13(12), С. 4433 - 4433

Опубликована: Дек. 10, 2021

The mechanisms of migraine pathogenesis are not completely clear, but 31P-nuclear magnetic resonance studies revealed brain energy deficit in migraineurs. As glycolysis is the main process production brain, mitochondria may play an important role pathogenesis. Nutrition aspect pathogenesis, as many migraineurs report food-related products triggers. Apart from approved anti-migraine drugs, vitamins and supplements considered prevention therapy, without strong supportive evidence. In this review, we summarize update information about nutrients that be for mitochondrial functions, production, oxidative stress, related to migraine. Additionally, present a brief overview caffeine alcohol, they often reported have ambiguous effects can supplement diet prevent and/or ameliorate riboflavin, thiamine, magnesium ions, niacin, carnitine, coenzyme Q10, melatonin, lipoic acid, pyridoxine, folate, cobalamin. They normal, healthy diet, which should adjusted individual needs determined mainly by physiological constitution organism. intake alcohol fine-tuned history their use, withdrawal these agents regular users become trigger.

Язык: Английский

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Mosaic dysfunction of mitophagy in mitochondrial muscle disease

Cell Metabolism, Год журнала: 2022, Номер 34(2), С. 197 - 208.e5

Опубликована: Янв. 13, 2022

Mitophagy is a quality control mechanism that eliminates damaged mitochondria, yet its significance in mammalian pathophysiology and aging has remained unclear. Here, we report mitophagy contributes to mitochondrial dysfunction skeletal muscle of aged mice human patients. The early disease stage characterized by fibers with central nuclei, enhanced around these nuclei. However, progressive halts disrupts lysosomal homeostasis. Interestingly, activated or halted occur mosaic manner even adjacent fibers, indicating cell-autonomous regulation. Rapamycin restores turnover, mTOR-dependence recycling advanced stage. Our evidence suggests (1) hallmark age-related pathology muscle, (2) halting explaining respiratory chain deficiency accumulation pathogenic mtDNA variants adult-onset diseases normal aging, (3) augmenting promising therapeutic approach for dysfunction.

Язык: Английский

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Current and Emerging Clinical Treatment in Mitochondrial Disease

Molecular Diagnosis & Therapy, Год журнала: 2021, Номер 25(2), С. 181 - 206

Опубликована: Март 1, 2021

Primary mitochondrial disease (PMD) is a group of complex genetic disorders that arise due to pathogenic variants in nuclear or genomes. Although PMD one the most prevalent inborn errors metabolism, it often exhibits marked phenotypic variation and can therefore be difficult recognise. Current treatment for revolves around supportive preventive approaches, with few disease-specific therapies available. However, over last decade there has been considerable progress our understanding both genetics pathophysiology PMD. This resulted development plethora new pharmacological non-pharmacological at varying stages development. Many these are currently undergoing clinical trials. review summarises latest emerging may become mainstream coming years. It distinct from other recent reviews field by comprehensively addressing therapy bench bedside perspective. We highlight current developing therapeutic landscape novel treatment, dietary supplementation, exercise training, device use, donation, tissue replacement gene therapy, hypoxic base editing.

Язык: Английский

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Metabolic regulation of somatic stem cells in vivo

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(6), С. 428 - 443

Опубликована: Фев. 28, 2022

Язык: Английский

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