Inflammation and aging: signaling pathways and intervention therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 8, 2023

Abstract Aging is characterized by systemic chronic inflammation, which accompanied cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there an urgent need for a systematic organization inflammaging through dimensionality reduction. Factors secreted senescent cells, known as senescence-associated secretory phenotype (SASP), promote inflammation can induce senescence in normal cells. At same time, accelerates immune resulting weakened function inability to clear cells inflammatory factors, creates vicious cycle senescence. Persistently elevated levels organs such bone marrow, liver, lungs cannot be eliminated leading damage aging-related Therefore, has been recognized endogenous factor elimination could potential strategy anti-aging. Here we discuss at molecular, cellular, organ, disease levels, review current aging models, implications cutting-edge single cell technologies, well anti-aging strategies. Since preventing alleviating diseases improving overall quality life are ultimate goals research, our highlights critical features mechanisms along with latest developments future directions providing theoretical foundation novel practical

Language: Английский

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Inflammasome activation at the crux of severe COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(11), P. 694 - 703

Published: Aug. 9, 2021

Language: Английский

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Pathogenesis of pneumonia and acute lung injury

Clinical Science, Journal Year: 2022, Volume and Issue: 136(10), P. 747 - 769

Published: May 1, 2022

Abstract Pneumonia and its sequelae, acute lung injury, present unique challenges for pulmonary critical care healthcare professionals, these have recently garnered global attention due to the ongoing Sars-CoV-2 pandemic. One limitation translational investigation of including most severe manifestation (acute respiratory distress syndrome, ARDS) has been heterogeneity resulting from clinical physiologic diagnosis that represents a wide variety etiologies. Recent efforts improved our understanding approach by defining sub-phenotypes ARDS although significant gaps in knowledge remain. Improving mechanistic injury common cause, infectious pneumonia, can advance precision targeted interventions. Here, we review pathogenesis pneumonia how infections disrupt homoeostasis, provide an overview microbial pathogenesis, microbiome, interventions demonstrated improve outcomes—or not—in human trials.

Language: Английский

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Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8062 - 8062

Published: Oct. 29, 2020

Through various pathways of cell death, degradation, and regulated extrusion, partial or complete genomes origins (e.g., host cells, fetal infiltrating viruses microbes) are continuously shed into human body fluids in the form segmented cell-free DNA (cfDNA) molecules. While genetic complexity total cfDNA is vast, development progressively efficient extraction, high-throughput sequencing, characterization via bioinformatics procedures, detection have resulted increasingly accurate partitioning profiling subtypes. Not surprisingly, analysis emerging as a powerful clinical tool many branches medicine. In addition, low invasiveness longitudinal sampling provides unprecedented access to study temporal genomic changes variety contexts. However, diversity also great source ambiguity poses significant experimental analytical challenges. For example, population bloodstream heterogeneous fluctuates dynamically, differs between individuals, exhibits numerous overlapping features despite often originating from different sources processes. Therefore, deeper understanding determining variables that impact properties crucial, however, thus far, largely lacking. this work we review recent historical research on active vs. passive release mechanisms estimate significance extent their contribution composition cfDNA.

Language: Английский

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Diversity and complexity of cell death: a historical review

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1573 - 1594

Published: Aug. 23, 2023

Abstract Death is the inevitable fate of all living organisms, whether at individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome nonfunctioning cells, as inflammation inevitably triggered in response damage. However, experimental evidence accumulated over past few decades has revealed different types that are genetically programmed eliminate unnecessary severely damaged cells may damage surrounding tissues. Several death, including apoptosis, necrosis, autophagic and lysosomal which classified pyroptosis, necroptosis, NETosis, inflammatory have been described years. Recently, several novel forms namely, mitoptosis, paraptosis, immunogenic entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, erebosis, discovered advanced our understanding its complexity. In this review, we provide historical overview discovery characterization highlight their diversity We also briefly discuss regulatory mechanisms underlying each type implications various physiological pathological contexts. This review provides comprehensive can leveraged develop therapeutic strategies for diseases.

Language: Английский

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Neutrophil extracellular traps in cancer

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 79, P. 91 - 104

Published: July 16, 2021

Language: Английский

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The Nexus of cfDNA and Nuclease Biology

Trends in Genetics, Journal Year: 2021, Volume and Issue: 37(8), P. 758 - 770

Published: May 15, 2021

Cell-free DNA (cfDNA) is a widely used noninvasive biomarker for diagnosis and prognosis of multiple disease states. Emerging evidence suggests that cfDNA might not just be passive waste products cell death but could have physiological pathological function in inflammation autoimmunity. The balance generation clearance may thus vital health disease. In particular, plasma nuclease activity has been linked to pathologies including cancer systemic lupus erythematosus (SLE) associated with profound changes the nonrandom fragmentation cfDNA. Lastly, this review, we explore effects factor B (DFFB), DNASE1L3, DNASE1 on levels their fragmentomic profiles, what these recent insights reveal about biology

Language: Английский

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NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 2, 2022

Infection with SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism COVID-19 immunopathy is recruitment activation neutrophils at infection site, which also predicts severity poor outcomes. The release neutrophil extracellular traps (NETs), occurring during a regulated form cell death known as NETosis, key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis NET generation have been observed in many patients, leading to unfavorable coagulopathy immunothrombosis. Moreover, excessive are now more widely recognized mediators additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes NET-producing (e.g., low-density granulocytes) explain biological importance NETs protein cargos COVID-19. addition, discuss mechanisms upregulating viral processes entry replication) well host pro-NET proinflammatory mediator release, platelet activation, autoantibody production). Furthermore, provide an update main findings immunothrombosis other COVID-19-related disorders, such aberrant immunity, neurological post syndromes including lung fibrosis, disorder, tumor progression, deteriorated chronic illness. Finally, address potential prospective treatment strategies target dysregulated formation via inhibition promotion degradation, respectively.

Language: Английский

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NLRP3 Inflammasome Assembly in Neutrophils Is Supported by PAD4 and Promotes NETosis Under Sterile Conditions

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: May 28, 2021

Neutrophil extracellular trap formation (NETosis) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome assembly are associated with a similar spectrum of human disorders. While NETosis is known to be regulated by peptidylarginine deiminase 4 (PAD4), role NLRP3 in was not addressed. Here, we establish that under sterile conditions cannonical participates NETosis. We show apoptosis-associated speck-like protein CARD (ASC) speck caspase-1 cleavage stimulated mouse neutrophils without LPS priming. PAD4 needed for optimal regulating ASC levels post-transcriptionally. Genetic ablation signaling resulted impaired NET formation, because supported both nuclear envelope plasma membrane rupture. Pharmacological inhibition either or also diminished Finally, deficiency lower density NETs thrombi produced stenosis-induced model deep vein thrombosis. Altogether, our results indicate PAD4-dependent implicate noninfectious vitro vivo .

Language: Английский

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Receptor-Mediated NETosis on Neutrophils

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 4, 2021

Neutrophil extracellular traps (NETs), a web-like structures containing chromatin, have significant role in assisting the capture and killing of microorganisms by neutrophils during infection. The specific engagement cell-surface receptors signaling molecules activates diverse intracellular cascades regulates neutrophil effector functions, including phagocytosis, reactive oxygen species release, degranulation, NET formation. However, overproduction NETs is closely related to occurrence inflammation, autoimmune disorders, non-canonical thrombosis tumor metastasis. Therefore, it necessary understand activation signals subsequent formation NETs, as well immune regulation. In this review, we provide an overview immunoreceptor-mediated regulation NETosis. pathways involved release infection or stimulation noninfectious substances are discussed detail. mechanisms which undergo NETosis help refine our views on roles protection diseases, providing theoretical basis for research NETs.

Language: Английский

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