The Intestinal Barrier Dysfunction as Driving Factor of Inflammaging

Nutrients, Год журнала: 2022, Номер 14(5), С. 949 - 949

Опубликована: Фев. 23, 2022

The intestinal barrier, composed of the luminal microbiota, mucus layer, and physical barrier consisting epithelial cells immune cells, latter residing underneath within plays a special role in health disease. While there is growing knowledge on changes to different layers associated with disease development, function also an important during aging. Besides composition cellular junctions, entire gastrointestinal physiology contributes essential age-related changes. This reflected by substantial differences microbial throughout life span. Even though it remains difficult define physiological distinguish them from early signs pathologies, studies centenarians provide insights into features longevity. reviewed this narrative review article might contribute definition strategies prevent development diseases elderly. Thus, targeted interventions improve overall will be prevention for healthy aging future.

Язык: Английский

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Emerging role of aging in the progression of NAFLD to HCC

Ageing Research Reviews, Год журнала: 2022, Номер 84, С. 101833 - 101833

Опубликована: Дек. 22, 2022

Язык: Английский

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AP‐1 is a regulatory transcription factor of inflammaging in the murine kidney and liver

Aging Cell, Год журнала: 2023, Номер 22(7)

Опубликована: Май 8, 2023

Aging is characterized by chronic low-grade inflammation in multiple tissues, also termed "inflammaging", which represents a significant risk factor for many aging-related diseases. However, the mechanisms and regulatory networks underlying inflammaging across different tissues have not yet been fully elucidated. Here, we profiled transcriptomes epigenomes of kidney liver from young aged mice found that activation inflammatory response conserved signature both tissues. Moreover, revealed links between transcriptome changes chromatin dynamics through integrative analysis identified AP-1 ETS family transcription factors (TFs) as potential regulators inflammaging. Further situ validation showed c-JUN (a member family) was mainly activated renal hepatic cells, while increased SPI1 mostly induced elevated infiltration macrophages, indicating these TFs Functional data demonstrated genetic knockdown Fos, major family, significantly attenuated kidneys livers. Taken together, our results signatures liver, providing novel targets development anti-aging interventions.

Язык: Английский

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Age-related changes in intestinal immunity and the microbiome

Journal of Leukocyte Biology, Год журнала: 2020, Номер 109(6), С. 1045 - 1061

Опубликована: Окт. 5, 2020

Abstract The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well education immune cells. Homeostasis gut maintained by interplay intestinal epithelium, cells, luminal Ags, and microbiota. well-being intrinsically linked to overall health host, perturbations this homeostasis can have severe impacts on local systemic health. One factor that causes disruptions in age, recent research has elucidated how critical systems within are altered during aging process. Intestinal stem cell proliferation, epithelial barrier function, microbiota, composition innate adaptive responses all advanced age. population continues expand worldwide, phenomenon referred “Silver Tsunami,” every effort must be made understand best prevent treat age-related maladies. Here, about changes observed system, interacts with influences other organs such liver, lung, brain reviewed. Better understanding these their impact multi-organ interactions will aid development therapies increase quality life aged individuals.

Язык: Английский

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Gastrointestinal permeability and kidney injury risk during hyperthermia in young and older adults

Experimental Physiology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 17, 2024

Abstract We tested whether older adults, compared with young exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine (32 ± 3 years) nine (72 participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via water‐perfused suit). Gastrointestinal was assessed multi‐sugar drink test containing lactulose, sucrose rhamnose. Blood urine samples assayed for markers intestinal barrier [plasma fatty acid binding protein (I‐FABP), plasma lipopolysaccharide (LBP) soluble cluster differentiation 14 (sCD14)], inflammation (serum cytokines), function (plasma creatinine cystatin C) [urine arithmetic product IGFBP7 TIMP‐2 (TIMP‐2 × IGFBP7), neutrophil gelatinase‐associated lipocalin molecule‐1]. The lactulose‐to‐rhamnose ratio increased in both adults (group‐wide: Δ0.11 0.11), but the excretion only (Δ1.7 1.5). Young showed similar increases LBP Δ0.65 0.89 µg/mL), no changes observed I‐FABP or sCD14. Heat stress caused Δ0.08 0.07 mg/dL), C Δ0.16 0.18 mg/L) urinary [group‐wide: Δ0.64 0.95 (pg/min) 2 ] adults. Thus, level used herein modest permeability, resulting mild inflammatory response Furthermore, our data indicate that might be more at risk gastroduodenal as evidenced larger to Finally, findings show impairs elevates injury; however, these responses are not modulated age.

Язык: Английский

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Impairments of intestinal arginine and NO metabolisms trigger aging-associated intestinal barrier dysfunction and ‘inflammaging'

Redox Biology, Год журнала: 2022, Номер 58, С. 102528 - 102528

Опубликована: Окт. 31, 2022

Aging is considered a state of low grade inflammation, occurring in the absence any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be target extend healthier status older adults. Here, we report that even healthy men bacterial endotoxemia prevalent. In addition, employing multiple mouse models, also show while microbiota composition changes significantly during aging, fecal transplantation old mice does not protect against aging-associated barrier dysfunction small intestine. Rather, NO and arginine metabolism mediated through arginase synthesis altered intestine aging mice. Treatment with inhibitor norNOHA prevented dysfunction, delayed onset senescence peripheral tissue e.g., liver. Intestinal metabolisms could prevention subsequently decline

Язык: Английский

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Intestinal epithelial injury and inflammation after physical work in temperate and hot environments in older men with hypertension or type 2 diabetes

Experimental Physiology, Год журнала: 2025, Номер unknown

Опубликована: Март 30, 2025

Abstract We tested whether older adults with well‐controlled type 2 diabetes or hypertension, compared age‐matched without chronic disease, exhibit greater intestinal damage, microbial translocation and inflammation during exertional heat stress. Twelve healthy men (age 59 years, SD 4 years), nine 60 5 years) hypertension walked for 180 min at 200 W/m in temperate conditions (wet‐bulb globe temperature 16°C) high‐heat stress 32°C). Serum fatty acid binding protein (IFABP), plasma soluble cluster of differentiation 14, lipopolysaccharide‐binding (LBP), interleukin‐6 tumour necrosis factor‐alpha were measured pre‐ postexercise after recovery. Total exercise duration was lower ( p ≤ 0.049), but core did not differ. All markers increased more versus < 0.002). In the heat, individuals had increases IFABP [+545 pg/mL (95% confidence interval: 222, 869)] LBP [+3.64 µg/mL (1.73, 5.56)] relative to control subjects 0.048), these resolved Despite reduced duration, hypertensive showed similar subjects. Our findings suggest that workers might have vulnerability heat‐induced gastrointestinal barrier disturbance downstream inflammatory responses when otherwise healthy, prolonged heat.

Язык: Английский

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Ginsenoside Rg1 ameliorates aging‑induced liver fibrosis by inhibiting the NOX4/NLRP3 inflammasome in SAMP8 mice

Molecular Medicine Reports, Год журнала: 2021, Номер 24(5)

Опубликована: Сен. 14, 2021

Aging is often accompanied by liver injury and fibrosis, eventually leading to the decline in function. However, mechanism of aging‑induced fibrosis still not fully understood, best our knowledge, there are currently no effective treatment options available for aging. Ginsenoside Rg1 (Rg1) has been reported exert potent anti‑aging effects due its potential antioxidant anti‑inflammatory activity. The present study aimed investigate protective effect underlying action senescence‑accelerated mouse prone 8 (SAMP8) mice treated 9 weeks. histopathological results showed that arrangement hepatocytes was disordered, vacuole‑like degeneration occurred majority cells, collagen IV TGF‑β1 expression levels, were detected via immunohistochemistry, also significantly upregulated SAMP8 group. markedly improved downregulated levels TGF‑β1. In addition, dihydroethylene staining western blotting reduced reactive oxygen species (ROS) IL‑1β, NADPH oxidase 4 (NOX4), p47phox, p22phox, phosphorylated‑NF‑κB, caspase‑1, apoptosis‑associated speck‑like protein containing a C‑terminal caspase recruitment domain NLR family pyrin 3 (NLRP3) inflammasome, which tissues elderly mice. conclusion, findings suggested may attenuate reducing NOX4‑mediated ROS oxidative stress inhibiting NLRP3 inflammasome activation.

Язык: Английский

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A Common UDP-Glucuronosyltransferase (UGT)1A Haplotype Is Associated With Accelerated Aging in Humanized Transgenic Mice

Oxidative Medicine and Cellular Longevity, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Background: Aging is characterized by the progressive decline of physiological functions and associated with an increasing risk for developing multiple age-related diseases. UDP-glucuronosyltransferase (UGT)1A enzymes detoxify a variety endo- xenobiotic reactive metabolites, thereby acting as indirect antioxidants. A common genetic UGT1A haplotype was shown to affect redox balance in humanized transgenic (htg) mice. Since oxidative stress main activator cellular senescence, we aimed investigate role variants process aging. Methods: HtgUGT1A-WT htgUGT1A-SNP mice were harvested at age either 12 weeks (young) or 18 months (aged). The effect aging examined analyzing expression activity, senescence markers, senescence-associated secretory phenotype (SASP) factors, well blood counts, serum parameter, histological staining. Results: In comparison aged htgUGT1A-WT mice, hepatic mRNA protein UGT activity significantly reduced Moreover, elderly exhibited increased levels stress, SASP peripheral leukocyte counts compared respective Consistent these findings, observed higher amounts collagen amyloid fibrils elevated β-galactosidase (SA-β-gal) sections liver obtained from Conclusion: Our data suggest accelerated caused haplotype. individuals carrying might exhibit altered metabolism drugs, which could necessitate dose adjustments.

Язык: Английский

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Cynarin attenuates LPS-induced endothelial inflammation via upregulation of the negative regulator MKP-3

Animal Cells and Systems, Год журнала: 2022, Номер 26(3), С. 119 - 128

Опубликована: Май 4, 2022

Clinical observations have revealed that non-resolving low-grade inflammation is linked to the pathogenesis of chronic inflammatory diseases, for example arthritis, atherosclerosis, Alzheimer's disease, diabetes, and kidney disease. Interestingly, low levels circulating lipopolysaccharides (LPS) derived from outer membrane gram-negative bacteria appear be one primary causes persistent inflammation. The inner surface blood vessels lined with endothelial cells; therefore, even LPS can directly activate these cells elicit specific cellular responses, such as an increase in expression cell adhesion molecules proinflammatory mediators. In cells, exposure results response through activation nuclear factor-kappa B (NF-κB) mitogen-activated protein kinases. Cynarin, a phytochemical found artichokes, has several pharmacological properties against present study, we discovered cynarin suppressed LPS-induced vascular molecule-1 mediators monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β EA.hy926 cells. Further, inhibited p38 NF-κB pathways by inducing negative regulator kinase phosphatase 3 (MKP-3) LPS-stimulated conclusion, alleviates upregulating MKP-3, NF-κB, it may therapeutic option treating inflammation-related diseases.

Язык: Английский

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