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Sökning: WFRF:(Shiels PG)

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  • Buchanan, S, et al. (författare)
  • Klotho, Aging, and the Failing Kidney
  • 2020
  • Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11, s. 560-
  • Tidskriftsartikel (refereegranskat)
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  • Carrero, JJ, et al. (författare)
  • Telomere biology alterations as a mortality risk factor in CKD
  • 2008
  • Ingår i: American journal of kidney diseases : the official journal of the National Kidney Foundation. - : Elsevier BV. - 1523-6838. ; 51:6, s. 1076-1077
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Craven, H, et al. (författare)
  • Socioeconomic position links circulatory microbiota differences with biological age
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 12629-
  • Tidskriftsartikel (refereegranskat)abstract
    • Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.
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  • Dai, L, et al. (författare)
  • Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage
  • 2020
  • Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 35:Suppl 2, s. 31-37
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population. Current clinical therapeutic strategies and novel treatments for VC have not yet been proven to prevent or reverse VC progression in patients with CKD. Knowledge of the fundamental mechanism underlying EVA is urgently needed to identify and develop novel and efficient therapeutic targets for VC and EVA. An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage–induced cellular senescence and ‘inflammaging’ may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2–related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging.
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  • Diaz-Gallo, LM, et al. (författare)
  • Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility
  • 2013
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:7, s. 1233-1238
  • Tidskriftsartikel (refereegranskat)abstract
    • The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc).Patients and methodsThe case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays.ResultsWe observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively).ConclusionsThese results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.
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  • Ebert, T, et al. (författare)
  • Ageing - Oxidative stress, PTMs and disease
  • 2022
  • Ingår i: Molecular aspects of medicine. - : Elsevier BV. - 1872-9452 .- 0098-2997. ; 86, s. 101099-
  • Tidskriftsartikel (refereegranskat)
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  • Ebert, T, et al. (författare)
  • Inflammation and Premature Ageing in Chronic Kidney Disease
  • 2020
  • Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.
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  • Hobson, S, et al. (författare)
  • Senescent Cells in Early Vascular Ageing and Bone Disease of Chronic Kidney Disease-A Novel Target for Treatment
  • 2019
  • Ingår i: Toxins. - : MDPI AG. - 2072-6651. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Together with bone-mineral disorders, premature vascular ageing is a common feature of the uremic phenotype. A detailed understanding of mechanisms involved remains unclear and warrants further research. Available treatment options for end stage renal disease are principally dialysis and organ transplantation, as other treatment alternatives have proven insufficient. Chronic kidney disease (CKD) has been proposed as a model of early vascular and bone ageing, with accumulating evidence supporting the contribution of cellular senescence and the senescence-associated secretory phenotype (SASP) to cardiovascular pathology in CKD. Correspondingly, novel therapies based around the use of senolytic compounds and nuclear factor-erythroid-2-related factor 2 (Nrf2) agonists, have been suggested as attractive novel treatment options. In this review, we detail the contribution of the uremic environment to these processes underpinning ageing and how these relate to vascular health.
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  • Kato, S, et al. (författare)
  • Telomere Attrition and Elongation after Chronic Dialysis Initiation in Patients with End-Stage Renal Disease
  • 2016
  • Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 41:1-3, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Aims:</i></b> To analyze changes in telomere length (TL) after dialysis initiation. <b><i>Methods:</i></b> In 59 Japanese incident dialysis patients, associations between TL in peripheral blood leukocytes, inflammatory biomarkers and nutritional status at baseline and changes in TL during 1 year of dialysis, were investigated. <b><i>Results:</i></b> Whereas relative TL decreased by 8.6% (median 14.4%), TL elongation occurred in 16 patients (27%). Change in TL (&#x0394;TL), defined as TL at 1 year minus TL at baseline, was associated with baseline TL (&#x03C1; = -0.70, p < 0.0001) and leukocyte count (&#x03C1; = 0.26, p = 0.044). In a logistic regression model, baseline TL (p < 0.0001) and leukocyte count (p = 0.047) were associated with &#x0394;TL. <b><i>Conclusions:</i></b> TL shortening was observed in most incident dialysis patients. In 16 of the 59 patients, TL elongation occurred, possibly reflecting a more robust biological aging in patients whose naïve leukocytes may have undergone less proliferation to replace lost leukocytes.
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  • Kooman, JP, et al. (författare)
  • Chronic kidney disease and premature ageing
  • 2014
  • Ingår i: Nature reviews. Nephrology. - : Springer Science and Business Media LLC. - 1759-507X .- 1759-5061. ; 10:12, s. 732-742
  • Tidskriftsartikel (refereegranskat)
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  • Kooman, JP, et al. (författare)
  • Inflammation and premature aging in advanced chronic kidney disease
  • 2017
  • Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 313:4, s. F938-F950
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called “inflammaging” in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed.
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  • Kooman, JP, et al. (författare)
  • The oxygen cascade in patients treated with hemodialysis and native high-altitude dwellers: lessons from extreme physiology to benefit patients with end-stage renal disease
  • 2021
  • Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 320:3, s. F249-F261
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients treated with hemodialysis (HD) repeatedly undergo intradialytic low arterial oxygen saturation and low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. HD treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, capillary rarefaction and reduced mitochondrial efficacy can further affect the balance between cellular oxygen supply and demand. Whereas it has been convincingly demonstrated that a reduced perfusion of heart and brain during HD contributes to organ damage, the significance of systemic hypoxia remains uncertain, although it may contribute to oxidative stress, systemic inflammation, and accelerated senescence. These abnormalities along the oxygen cascade of patients treated with HD appear to be diametrically opposite to the situation in Tibetan highlanders and Sherpa, whose physiology adapted to the inescapable hypobaric hypoxia of their living environment over many generations. Their adaptation includes pulmonary, vascular, and metabolic alterations with enhanced capillary density, nitric oxide production, and mitochondrial efficacy without oxidative stress. Improving the tissue oxygen supply in patients treated with HD depends primarily on preventing hemodynamic instability by increasing dialysis time/frequency or prescribing cool dialysis. Whether dietary or pharmacological interventions, such as the administration of L-arginine, fermented food, nitrate, nuclear factor erythroid 2-related factor 2 agonists, or prolyl hydroxylase 2 inhibitors, improve clinical outcome in patients treated with HD warrants future research.
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  • Ledeganck, KJ, et al. (författare)
  • MicroRNAs in AKI and Kidney Transplantation
  • 2019
  • Ingår i: Clinical journal of the American Society of Nephrology : CJASN. - 1555-905X. ; 14:3, s. 454-468
  • Tidskriftsartikel (refereegranskat)
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  • Mafra, D, et al. (författare)
  • Food for healthier aging: power on your plate
  • 2024
  • Ingår i: Critical reviews in food science and nutrition. - : Informa UK Limited. - 1549-7852 .- 1040-8398. ; 64:3, s. 603-616
  • Tidskriftsartikel (refereegranskat)
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  • Moreira, LDG, et al. (författare)
  • Cinnamon: an aromatic condiment applicable to chronic kidney disease
  • 2023
  • Ingår i: Kidney research and clinical practice. - : The Korean Society of Nephrology. - 2211-9132 .- 2211-9140. ; 42:1, s. 4-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Cinnamon, a member of the Lauraceae family, has been widely used as a spice and traditional herbal medicine for centuries and hasshown beneficial effects in cardiovascular disease, obesity, and diabetes. However, its effectiveness as a therapeutic intervention forchronic kidney disease (CKD) remains unproven. The bioactive compounds within cinnamon, such as cinnamaldehyde, cinnamicacid, and cinnamate, can mitigate oxidative stress, inflammation, hyperglycemia, gut dysbiosis, and dyslipidemia, which are commoncomplications in patients with CKD. In this narrative review, we assess the mechanisms by which cinnamon may alleviate complicationsobserved in CKD and the possible role of this spice as an additional nutritional strategy for this patient group.
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