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

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Jan. 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.

Language: Английский

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SIRT1 Activation by Natural Phytochemicals: An Overview

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 7, 2020

Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD+ as a cofactor. reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead tissue-specific degenerative events involved in the development several human pathologies, including cancer, neurodegeneration, cardiovascular disease. The most studied member this enzymes sirtuin 1 (SIRT1), associated with increasing insulin sensitivity. SIRT1 has been implicated both tumorigenic anticancer processes, regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders metabolism. Via regulation p53 deacetylation modulation autophagy, cellular response caloric restriction lifespan extension. In recent years, scientific interest focusing identification modulators led discovery novel small molecules targeting activity. This review will examine compounds natural origin recently found upregulate activity, such polyphenolic products fruits, vegetables, plants resveratrol, fisetin, quercetin, curcumin. We also discuss potential therapeutic effects these prevention treatment disorders, particular emphasis impact.

Language: Английский

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Senescence in Mesenchymal Stem Cells: Functional Alterations, Molecular Mechanisms, and Rejuvenation Strategies

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: May 5, 2020

Mesenchymal stem cells (MSCs) are multipotent capable of self-renewal and differentiation, mounting evidence has reported their therapeutic values in various clinical situations. However, as they age, MSCs gradually lose regenerative potential, while the occurrence cellular dysfunction strongly arises. On one hand, cell aging exhaustion considered hallmarks organismal functional attrition. other do not proliferate infinitely, but undergo only a limited number population doublings process termed senescence. Senescence greatly hampers application MSC since it requires an extensive expansion to get substantial for therapy. Here we review current knowledge phenotypic characteristics senescent MSCs, well molecular mechanisms that involved strategies rejuvenate MSCs. This may offer opportunities prevent, postpone, or even reverse kinetics with which aged.

Language: Английский

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Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies

Stem Cells Translational Medicine, Journal Year: 2022, Volume and Issue: 11(4), P. 356 - 371

Published: Jan. 29, 2022

Aging is a multifaceted and complicated process, manifested by decline of normal physiological functions across tissues organs, leading to overt frailty, mortality, chronic diseases, such as skeletal, cardiovascular, cognitive disorders, necessitating the development practical therapeutic approaches. Stem cell aging one theories organismal aging. For decades, mesenchymal stem/stromal cells (MSCs) have been regarded viable ideal source for stem cell-based therapy in anti-aging treatment due their outstanding clinical characteristics, including easy accessibility, simplicity isolation, self-renewal proliferation ability, multilineage differentiation potentials, immunomodulatory effects. Nonetheless, evidenced numerous studies, MSCs undergo functional deterioration gradually lose stemness with systematic age vivo or extended culture vitro, limiting applications. Even though our understanding processes behind MSC senescence remains unclear, significant progress has achieved elucidating aspects age-related phenotypic changes possible mechanisms driving senescence. In this review, we aim summarize current knowledge morphological, biological, stem-cell marker alterations MSCs, cellular molecular that underlie senescence, recent made regarding innovative techniques rejuvenate senescent combat aging, particular focus on interplay between niche well translational relevance. Also, provide some promising novel directions future research concerning

Language: Английский

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Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: Jan. 29, 2019

Sirtuins, class III histone deacetylases, are differentially expressed in several human cancers, where they display both oncogenic and tumor-suppressive properties depending on cellular context experimental conditions. Sirtuins involved many important biological processes play a critical role cancer initiation, promotion progression. A growing body of evidence indicates the involvement sirtuins regulating three tumor processes: epithelial-to-mesenchymal transition (EMT), invasion metastasis. Many responsible for metabolic reprogramming drug resistance by inactivating cell death pathways promoting uncontrolled proliferation. In this review, we summarize current knowledge discuss their puzzling dual function as suppressors promoters, future development novel tailored sirtuin-based therapies.

Language: Английский

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Sirtuins, resveratrol and the intertwining cellular pathways connecting them

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 88, P. 101936 - 101936

Published: April 26, 2023

Language: Английский

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When fats commit crimes: fatty acid metabolism, cancer stemness and therapeutic resistance

Cancer Communications, Journal Year: 2018, Volume and Issue: 38(1), P. 1 - 12

Published: July 11, 2018

Abstract The role of fatty acid metabolism, including both anabolic and catabolic reactions in cancer has gained increasing attention recent years. Many studies have shown that aberrant expression the genes involved synthesis or oxidation correlate with malignant phenotypes metastasis, therapeutic resistance relapse. Such are also strongly associated presence a small percentage unique cells among total tumor cell population. This distinct group may ability to self‐renew propagate be able develop therapies independent genetic alterations. Therefore, these referred as stem cells/tumor‐initiating cells/drug‐tolerant persisters, which often refractory treatment difficult target. Moreover, interconversion between persisters occur makes even more challenging. review highlights findings on relationship stemness prompts discussion about potential mechanisms by metabolism regulates fate resistance.

Language: Английский

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Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function

Clinica Chimica Acta, Journal Year: 2020, Volume and Issue: 508, P. 33 - 42

Published: April 27, 2020

Language: Английский

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HDAC inhibitors as antifibrotic drugs in cardiac and pulmonary fibrosis

Therapeutic Advances in Chronic Disease, Journal Year: 2019, Volume and Issue: 10

Published: Jan. 1, 2019

Fibrosis usually results from dysregulated wound repair and is characterized by excessive scar tissue. It a complex process with unclear mechanisms. Accumulating evidence indicates that epigenetic alterations, including histone acetylation, play pivotal role in this process. Histone acetylation governed acetyltransferases (HATs) deacetylases (HDACs). HDACs are enzymes remove the acetyl groups both nonhistone proteins. Aberrant HDAC activities observed fibrotic diseases, cardiac pulmonary fibrosis. inhibitors (HDACIs) molecules block functions. HDACIs have been studied extensively variety of tumors. Currently, there four approved US Food Drug Administration for cancer treatment yet none diseases. Emerging vitro vivo preclinical studies has presented beneficial effects preventing or reversing fibrogenesis. In review, we summarize latest findings roles pathogenesis fibrosis highlight potential applications these two

Language: Английский

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The roles of sirtuins family in cell metabolism during tumor development

Seminars in Cancer Biology, Journal Year: 2018, Volume and Issue: 57, P. 59 - 71

Published: Nov. 16, 2018

Language: Английский

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