Cellular senescence and senolytics: the path to the clinic

Nature Medicine, Год журнала: 2022, Номер 28(8), С. 1556 - 1568

Опубликована: Авг. 1, 2022

Язык: Английский

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Mitochondrial DNA Release in Innate Immune Signaling

Annual Review of Biochemistry, Год журнала: 2023, Номер 92(1), С. 299 - 332

Опубликована: Март 31, 2023

According to the endosymbiotic theory, most of DNA original bacterial endosymbiont has been lost or transferred nucleus, leaving a much smaller (∼16 kb in mammals), circular molecule that is present-day mitochondrial (mtDNA). The ability mtDNA escape mitochondria and integrate into nuclear genome was discovered budding yeast, along with genes regulate this process. Mitochondria have emerged as key regulators innate immunity, it now recognized released cytoplasm, outside cell, circulation activates multiple immune signaling pathways. Here, we first review mechanisms through which including several inducible pores defective mitophagy autophagy. Next, cover how different forms activate specific nucleic acid sensors inflammasomes. Finally, discuss intracellular extracellular release, circulating cell-free promotes systemic inflammation, are implicated human diseases, viral infections, senescence aging.

Язык: Английский

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The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

Antioxidants, Год журнала: 2022, Номер 11(7), С. 1224 - 1224

Опубликована: Июнь 22, 2022

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial protective several physiological processes, excessive senescent burden has been involved various pathological conditions including aging, tissue dysfunction chronic diseases. Oxidative stress (OS) can drive due a loss balance between pro-oxidant stimuli antioxidant defences. Therefore, the identification characterization compounds capable preventing or counteracting phenotype major interest. However, despite considerable number studies, comprehensive overview main molecules OS-induced still lacking. Here, besides brief description molecular mechanisms implicated OS-mediated we review discuss role enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur nitrogen non-protein molecules, minerals, flavonoids, non-flavonoids with anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.

Язык: Английский

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Cellular Senescence and Ageing: Mechanisms and Interventions

Frontiers in Aging, Год журнала: 2022, Номер 3

Опубликована: Март 29, 2022

The influence of the activation a cellular phenotype termed senescence and it’s importance in ageing age-related diseases is becoming more evident. In fact, there huge effort to tackle these via therapeutic drugs targeting senescent cells named senolytics. However, clearer understanding how activated it has on specific types tissues needed. Here, we describe general triggers characteristics senescence. addition, different diseases.

Язык: Английский

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H3K18 lactylation of senescent microglia potentiates brain aging and Alzheimer's disease through the NFκB signaling pathway

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Сен. 11, 2023

Cellular senescence serves as a fundamental and underlying activity that drives the aging process, it is intricately associated with numerous age-related diseases, including Alzheimer's disease (AD), neurodegenerative aging-related disorder characterized by progressive cognitive impairment. Although increasing evidence suggests senescent microglia play role in pathogenesis of AD, their exact remains unclear. In this study, we quantified levels lactic acid microglia, hippocampus tissues naturally aged mice AD models (FAD4T APP/PS1). We found were significantly elevated these cells compared to corresponding counterparts, which increased level pan histone lysine lactylation (Kla). aslo identified all Kla sites both H3K18 (H3K18la) Pan-Kla up-regulated modeling mice. demonstrated enhanced H3K18la directly stimulates NFκB signaling pathway binding promoter Rela (p65) NFκB1(p50), thereby upregulating senescence-associated secretory phenotype (SASP) components IL-6 IL-8. Our study provides novel insights into physiological function epigenetic regulatory mechanism regulates brain AD. Specifically, have H3K18la/NFκB axis critical player process modulating Targeting may be potential therapeutic strategy for delaying blunting SASP.

Язык: Английский

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PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy

Nature Metabolism, Год журнала: 2023, Номер 5(11), С. 1887 - 1910

Опубликована: Окт. 30, 2023

Abstract Senescent cells remain metabolically active, but their metabolic landscape and resulting implications underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. display a PDK4-dependent increase aerobic glycolysis enhanced lactate production maintain mitochondrial respiration redox activity, thus adopting special form reprogramming. Medium from PDK4 + promotes the malignancy recipient cancer vitro, whereas inhibition causes tumor regression vivo. We find that reactive oxygen species via NOX1 to drive senescence-associated secretory phenotype, suppression reduces DNA damage severity restrains phenotype. In preclinical trials, alleviates physical dysfunction prevents age-associated frailty. Together, our study confirms hypercatabolic nature senescent reveals link between cellular production, possibly, age-related pathologies, including not limited cancer.

Язык: Английский

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Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement

ACS Chemical Neuroscience, Год журнала: 2023, Номер 15(1), С. 1 - 30

Опубликована: Дек. 14, 2023

Aging is a dynamic, time-dependent process that characterized by gradual accumulation of cell damage. Continual functional decline in the intrinsic ability living organisms to accurately regulate homeostasis leads increased susceptibility and vulnerability diseases. Many efforts have been put forth understand prevent effects aging. Thus, major cellular molecular hallmarks aging identified, their relationships age-related diseases malfunctions explored. Here, we use data from CAS Content Collection analyze publication landscape recent aging-related research. We review advances knowledge delineate trends research advancements on factors attributes across time geography. also current concepts related molecular, cellular, organismic level, age-associated diseases, with attention brain health, as well biochemical processes associated Major outlined, correlations features are hope this will be helpful for apprehending field mechanisms progression, an effort further solve remaining challenges fulfill its potential.

Язык: Английский

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Oxidative Stress-Induced Cellular Senescence: Is Labile Iron the Connecting Link?

Antioxidants, Год журнала: 2023, Номер 12(6), С. 1250 - 1250

Опубликована: Июнь 10, 2023

Cellular senescence, a cell state characterized by generally irreversible cycle arrest, is implicated in various physiological processes and wide range of age-related pathologies. Oxidative stress, condition caused an imbalance between the production elimination reactive oxygen species (ROS) cells tissues, common driver cellular senescence. ROS encompass free radicals other molecules formed as byproducts metabolism, which exhibit varying chemical reactivity. A prerequisite for generation strong oxidizing that can damage macromolecules impair function availability labile (redox-active) iron, catalyzes formation highly radicals. Targeting iron has been proven effective strategy to counteract adverse effects ROS, but evidence concerning senescence sparse. In present review article, we discuss aspects oxidative stress-induced with special attention potential implication iron.

Язык: Английский

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Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases

Ageing Research Reviews, Год журнала: 2024, Номер 97, С. 102294 - 102294

Опубликована: Апрель 5, 2024

Язык: Английский

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Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease

Cells, Год журнала: 2024, Номер 13(4), С. 353 - 353

Опубликована: Фев. 17, 2024

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are primary cause death worldwide, with an immense impact on patient quality life and disability. According to World Health Organization, CVD takes estimated 17.9 million lives each year, where more than four out five deaths due attacks strokes. In decades come, increased prevalence age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular disease, failure (HF) will contribute even greater health economic burden global average expectancy increases consequently world’s population continues age. Considering this, it is important focus our research efforts understanding fundamental mechanisms underlying CVD. this review, we cellular senescence mitochondrial dysfunction, which have long been established We also assess recent advances in targeting dysfunction including energy starvation oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, therapies that influence both therefore perhaps represent strategies most clinical potential, range, utility.

Язык: Английский

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