Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging

JBMR Plus, Journal Year: 2022, Volume and Issue: 6(11)

Published: Sept. 30, 2022

Extracellular vesicles (EVs), including exosomes and microvesicles, are released by numerous cell types. EVs now acknowledged as playing a critical role in cell-cell communication healthy aging well age-related diseases. Recently it was shown that senescence, key hallmark of aging, increases the secretion EVs. Moreover, can transport proteins microRNAs (miRNAs) components senescence-associated secretory phenotype (SASP). Here we review evidence SASP-related miRNAs involved musculoskeletal degeneration with aging. Specifically, senescence-related elevated skeletal muscle myocytes fibro-adipogenic progenitor cells disuse atrophy, respectively. Many these same detected from synovial fluid patients osteoarthritis, contribute to cartilage degeneration. Finally, secreted bone marrow-derived stem (stromal) impacting neighboring hematopoietic circulating blood. The miRNA mir-34a, which is known target Wnt Notch pathways survival factors Sirt1 Bcl2, human animal subjects loss, osteoarthritis. These findings suggest suppressing EV-derived, miRNAs, such miR-34a, or increasing levels competing endogenous long noncoding RNAs, MALAT1 inhibit may help improve function © 2022 Authors. JBMR Plus published Wiley Periodicals LLC on behalf American Society for Bone Mineral Research.

Language: Английский

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Vascular calcification in CKD: New insights into its mechanisms

Journal of Cellular Physiology, Journal Year: 2023, Volume and Issue: 238(6), P. 1160 - 1182

Published: June 1, 2023

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and contributes to an increased risk cardiovascular morbidity mortality. However, effective therapies are still unavailable at present. It has been well established that VC associated with CKD not passive process calcium phosphate deposition, but actively regulated cell-mediated shares many similarities bone formation. Additionally, numerous studies have suggested patients specific factors contributors the development VC, such as hyperphosphatemia, uremic toxins, oxidative stress inflammation. Although research efforts in past decade greatly improved our knowledge multiple mechanisms involved CKD-related questions remain unanswered. Moreover, from demonstrated epigenetic modifications abnormalities, DNA methylation, histone noncoding RNAs, play important role regulation VC. This review seeks provide overview pathophysiological molecular CKD, mainly focusing on involvement initiation progression aim develop promising for events future.

Language: Английский

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Vascular Aging and Atherosclerosis: A Perspective on Aging

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological clinical research has demonstrated an intimate connection between AS, candidate mechanisms still require thorough examination. This review adopts aging-centric perspective to deepen comprehension intricate relationship biological aging, vascular cell senescence, AS. Various aging-related physiological factors influence physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, insulin resistance. These cause endothelial dysfunction, barrier damage, sclerosis, inflammation for VA promote AS via distinct or shared pathways. Furthermore, increase senescent cells inside tissues, caused by genetic dysregulation, secretome changes, epigenetic modifications, might be primary VA.

Language: Английский

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Micro-RNA profiles of pathology and resilience in posterior cingulate cortex of cognitively intact elders

Brain Communications, Journal Year: 2024, Volume and Issue: 6(2)

Published: Jan. 1, 2024

Abstract The posterior cingulate cortex (PCC) is a key hub of the default mode network underlying autobiographical memory retrieval, which falters early in progression Alzheimer’s disease (AD). We recently performed RNA sequencing post-mortem PCC tissue samples from 26 elderly Rush Religious Orders Study participants who came to autopsy with an ante-mortem diagnosis no cognitive impairment but collectively displayed range Braak I–IV neurofibrillary tangle stages. Notably, cognitively unimpaired subjects displaying high stages may represent resilience AD pathology. Transcriptomic data revealed elevated synaptic and ATP-related gene expression Stages III/IV compared I/II, suggesting these pathways be related resilience. also mined profiles for small non-coding micro-RNAs (miRNAs), regulate mRNA stability underexplored potential mechanism through fine-tuning within complex cellular networks. Twelve miRNAs were identified as differentially expressed between I/II III/IV. However, extent levels all associated subject demographics, neuropsychological test performance and/or neuropathological diagnostic criteria this cohort was not explored. Here, we report that total 667 are significantly (rho > 0.38, P < 0.05) variables. There significant positive correlations miRNA age, perceptual orientation speed. By contrast, higher correlated negatively semantic episodic memory. Higher 15 lower I–II 47 III–IV, additional mechanistic influences Pathway analysis showed enrichment operating lysine degradation fatty acid synthesis metabolism. Finally, demonstrated 12 resilience-related versus predicted mRNAs amyloid processing, tau inflammation. In summary, demonstrate dynamic state wherein differential intact elders. posit relationships inform transcriptional alterations relevant protective (resilience) or pathogenic (pre-clinical prodromal) responses pathogenesis thus therapeutic targets.

Language: Английский

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Regulatory RNAs in immunosenescence

Immunity Inflammation and Disease, Journal Year: 2024, Volume and Issue: 12(3)

Published: March 1, 2024

Abstract Background Immunosenescence is a multifactorial stress response to different intrinsic and extrinsic insults that cause immune deterioration accompanied by genomic or epigenomic perturbations. It now widely recognized genes proteins contributing in the process of immunosenescence are regulated various noncoding (nc) RNAs, including microRNAs (miRNAs), long ncRNAs, circular RNAs. Aims This review article aimed evaluate regulatore RNAs roles immunosenescence. Methods We analyzed publications were focusing on regulatory several aspects Results In setting, ncRNAs have been found play at both transcriptional post‐transcriptional levels. These factors cooperate regulate initiation gene expression programs sustaining senescence phenotype proinflammatory responses. Conclusion complex with pivotal alterations function occurring age. The extensive network drive immunosenescence‐related features mainly directed variety such as miRNAs, lncRNAs, circRNAs. Latest findings about regulation innate adaptive cells well their role pathways, provide better understanding

Language: Английский

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microRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician’s Perspective

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15645 - 15645

Published: Dec. 9, 2022

Ischemic stroke (IS) related to atherosclerosis of large arteries is one the leading causes mortality and disability in developed countries. Atherosclerotic internal carotid artery stenosis (ICAS) contributes 20% all cerebral ischemia cases. Nowadays, prevention treatment measures aim at controlling risk factors, or interventional (surgical endovascular) management mature occlusive lesions. There a definite lack established circulating biomarkers which, once modulated, could prevent development atherosclerosis, consequently carotid-artery-related IS. Recent studies emphasize that microRNA (miRNA) are emerging particles potentially play pivotal role this approach. some research on association between expression small non-coding microRNAs with plaque vulnerability. However, data remain inconsistent. In addition, major atherosclerotic were conducted cell culture animal models; very few humans, whereas accumulating evidence demonstrates it cannot be automatically extrapolated processes humans. Therefore, paper aims review current knowledge how miRNA participate process formation rupture, as well occurrence. We discuss potential target used prognostic therapeutic tool.

Language: Английский

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Cardiovascular complications of diabetes: role of non-coding RNAs in the crosstalk between immune and cardiovascular systems

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: May 24, 2023

Diabetes mellitus, a group of metabolic disorders characterized by high levels blood glucose caused insulin defect or impairment, is major risk factor for cardiovascular diseases and related mortality. Patients with diabetes experience state chronic intermittent hyperglycemia resulting in damage to the vasculature, leading micro- macro-vascular diseases. These conditions are associated low-grade inflammation accelerated atherosclerosis. Several classes leukocytes have been implicated diabetic impairment. Although molecular pathways through which elicits an inflammatory response attracted significant attention, how they contribute altering homeostasis still incompletely understood. In this respect, non-coding RNAs (ncRNAs) largely under-investigated class transcripts that may play fundamental role. This review article gathers current knowledge on function ncRNAs crosstalk between immune cells context complications, highlighting influence biological sex such mechanisms exploring potential role as biomarkers targets treatments. The discussion closes offering overview involved increased suffered patients facing Sars-CoV-2 infection.

Language: Английский

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γ‐glutamylcysteine alleviates insulin resistance and hepatic steatosis by regulating adenylate cyclase and IGF‐1R/IRS1/PI3K/Akt signaling pathways

The Journal of Nutritional Biochemistry, Journal Year: 2023, Volume and Issue: 119, P. 109404 - 109404

Published: June 11, 2023

Language: Английский

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Hippocampal microRNA-181a overexpression participates in anxiety and ethanol related behaviors via regulating the expression of SIRT-1

Physiology & Behavior, Journal Year: 2025, Volume and Issue: unknown, P. 114839 - 114839

Published: Feb. 1, 2025

Language: Английский

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MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute loss, but high treatment burden and efficacy with chronic therapy highlight need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as key regulator aging age-related diseases, its role neovascular AMD unclear. In an injury-induced murine CNV model, we discovered miR-34a promoted pathological angiogenesis, without altering expression Vegfa or receptor Kdr, canonical regulators CNV. Mechanistically, directly targets inhibits transcription KLF2 thereby upregulating pro-angiogenic factors CXCR4 CXCL12. Finally, show exacerbates aged mice expressed lesions excised from wet patients. These findings establish causal link between AMD. Identification molecular mechanism involved pathogenesis prevalent debilitating ocular disease.

Language: Английский

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