The impact of senescence on muscle wasting in chronic kidney disease

Journal of Cachexia Sarcopenia and Muscle, Год журнала: 2022, Номер 14(1), С. 126 - 141

Опубликована: Ноя. 9, 2022

Abstract Background Muscle wasting is a common complication of chronic kidney disease (CKD) that associated with higher mortality. Although the mechanisms myofibre loss in CKD has been widely studied, contribution muscle precursor cell (MPC) senescence remains poorly understood. Senescent MPCs no longer proliferate and can produce proinflammatory factors or cytokines. In this study, we tested hypothesis secretory phenotype (SASP) contributes to CKD‐induced atrophy weakness. Methods was induced mice by 5/6th nephrectomy. Kidney function, size, function were measured, markers atrophy, inflammation, evaluated using immunohistochemistry, immunoblots, qPCR. To study impact senescence, senolytics cocktail dasatinib + quercetin (D&Q) given orally for 8 weeks. investigate at cellular level, primary incubated serum from control subjects. The roles specific proteins MPC studied adenoviral transduction, siRNA, plasmid transfection. Results hindlimb muscles mice, (i) biomarker SA‐β‐gal sharply increased (~30‐fold); (ii) DNA damage response marker γ‐H2AX 1.9‐fold; (iii) pathway p21 p16 INK4a 1.99‐fold 2.82‐fold, respectively (all values, P < 0.05), whereas p53 unchanged. γ‐H2AX, p21, INK4A negatively correlated 0.05 gastrocnemius weight, suggesting causal relationship atrophy. Administration weeks eliminated disease‐related elevation , abolished positive SA‐β‐gal, depressed high levels SASP cytokines, TNF‐α, IL‐6, IL‐1β, IFN 0.05). Skeletal cross‐sectional area, grip improved receiving D&Q. Markers protein degradation, dysfunction also attenuated D&Q treatment compared vehicle nephrectomy Uraemic cultured MPCs. Overexpression FoxO1a number senescent cells, siRNA prevented uraemic serum‐induced ( Conclusions are likely contribute development during producing inflammatory Limiting ameliorated strength vivo restored functions. These results suggest potential new therapeutic targets improve health CKD.

Язык: Английский

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Induction of Accelerated Aging in a Mouse Model

Cells, Год журнала: 2022, Номер 11(9), С. 1418 - 1418

Опубликована: Апрель 22, 2022

With the global increase of elderly population, improvement treatment for various aging-related diseases and extension a healthy lifespan have become some most important current medical issues. In order to understand developmental mechanisms aging disorders, animal models are essential conduct relevant studies. Among them, mice one prevalently used model animals studies due their high similarity humans in terms genetic background physiological structure, as well short ease reproduction. This review will discuss common emerging mouse accelerated related chronic recent years, with aim serving reference future application fundamental translational research.

Язык: Английский

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Blood–brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Март 15, 2022

Abstract Kidney failure and associated uraemia have implications for the cardiovascular system, brain, blood–brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, gut-blood (GBB) disruption trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions modulation via TMAO were assessed. Serum from female male haemodialysis (HD) patients, controls, used measure BDNF NSE enzyme-linked immunosorbent assays, mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies transplant recipients, microvascular expression proteins (claudin-5, occludin, JAM-1), control microvasculature effects. HD patients versus had significantly lower higher serum levels NSE, respectively. In CKD reduced claudin-5, JAM-1 observed. Incubation with decreased all microvasculature. Uraemia affects GBB resulting altered circulating TMAO, respectively, it also reduces that confer maintenance. serves as a potential candidate alter integrity CKD.

Язык: Английский

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Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

Circulation Research, Год журнала: 2023, Номер 132(8), С. 950 - 969

Опубликована: Апрель 13, 2023

The pathophysiology of vascular disease is linked to accelerated biological aging and a combination genetic, lifestyle, biological, environmental risk factors. Within the scenario uncontrolled artery wall processes, CKD (chronic kidney disease) stands out as valid model for detailed structural, functional, molecular studies this process. cardiorenal syndrome relates detrimental bidirectional interplay between cardiovascular system. In addition established factors, group patients subjected plethora other emerging such inflammation, oxidative stress, mitochondrial dysfunction, vitamin K deficiency, cellular senescence, somatic mutations, epigenetic modifications, increased apoptosis. A better understanding mechanisms through which uremic milieu triggers maintains early has provided important new clues on inflammatory pathways factors alike, altered behavior cells in arterial wall. Advances biology opens avenues novel pharmacological nutritional therapeutic interventions. Such strategies hold promise improve future prevention treatment not only but also elderly general population.

Язык: Английский

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Early aging and premature vascular aging in chronic kidney disease

Clinical Kidney Journal, Год журнала: 2023, Номер 16(11), С. 1751 - 1765

Опубликована: Апрель 6, 2023

ABSTRACT Aging is the progressive decline of body functions and a number chronic conditions can lead to premature aging characterized by frailty, diseased vasculature, osteoporosis, muscle wasting. One major associated with accelerated kidney disease (CKD), which also result in early vascular stiffening arteries. Premature CKD patients has been considered as marker prognosis mortality cardiovascular morbidity therefore requires further attention. Oxidative stress, inflammation, advanced glycation end products, fructose, an aberrant gut microbiota contribute development patients. There are several key molecular pathways molecules play role including nuclear factor erythroid 2-related 2 (Nrf-2), AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), klotho. Potential therapeutic strategies target these pathways. Future studies needed better understand importance develop alternatives for conditions.

Язык: Английский

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Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage

Nephrology Dialysis Transplantation, Год журнала: 2020, Номер 35(Supplement_2), С. ii31 - ii37

Опубликована: Янв. 3, 2020

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 (EVA) process mediated medial calcification (VC) hallmark senescence as well strong predictor morbidity mortality in the CKD population. Current therapeutic strategies novel treatments for VC have not yet been proven to prevent or reverse progression patients with CKD. Knowledge fundamental mechanism underlying EVA urgently needed identify develop efficient targets EVA. An accumulating body evidence indicates that deoxyribonucleic acid (DNA) damage-induced cellular 'inflammaging' may largely contribute such pathological conditions Growing shows nuclear factor erythroid 2-related 2 (NRF2) signalling vitamin K play crucial role counteracting oxidative stress, DNA damage, inflammaging, whereby NRF2 activation supplementation provide treatment target In this review we discuss link between context CKD, focus on damage signalling, inflammaging.

Язык: Английский

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Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Cells, Год журнала: 2020, Номер 9(1), С. 195 - 195

Опубликована: Янв. 13, 2020

Aging is one of the hottest topics in biomedical research. Advances research and medicine have helped to preserve human health, leading an extension life expectancy. However, irreversible process that accompanied by development aging-related conditions such as weakness, slower metabolism, stiffness vessels. It also debated aging can be considered actual disease with aging-derived comorbidities, including cancer or cardiovascular disease. Currently, disorders, atherosclerosis, are premature represent first causes death developed countries, accounting for 31% annual deaths globally. Emerging evidence has identified hypoxia-inducible factor-1α a critical transcription factor essential role pathology, particular, regulating cellular senescence associated aging. In this review, we will focus on regulation mediated age-related pathologies, particular emphasis crosstalk between endothelial vascular cells age-associated atherosclerotic lesions. More specifically, characteristics mechanisms which within wall, cells, achieve senescent phenotype.

Язык: Английский

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Vascular Calcification in Chronic Kidney Disease: An Update and Perspective

Aging and Disease, Год журнала: 2022, Номер 13(3), С. 673 - 673

Опубликована: Янв. 1, 2022

Chronic kidney disease is a devastating condition resulting from irreversible loss of nephron numbers and function leading to end-stage renal mineral disorders. Vascular calcification, an ectopic deposition calcium-phosphate salts in blood vessel walls heart valves, independent risk factor cardiovascular morbidity mortality chronic disease. Moreover, aging related metabolic disorders are essential factors for vascular calcification. Marked progress has been recently made understanding treating calcification However, there paucity systematic reviews summarizing this progress, investigating unresolved issues warranted. In review, we aimed overview the underlying mechanisms diseases discuss impact on pathophysiology Additionally, summarized potential clinical diagnostic biomarkers therapeutic applications with This review may offer new insights into pathogenesis, diagnosis, intervention

Язык: Английский

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Combating chronic kidney disease-associated cachexia: A literature review of recent therapeutic approaches

BMC Nephrology, Год журнала: 2025, Номер 26(1)

Опубликована: Март 11, 2025

In 2008, the Society on Sarcopenia, Cachexia, and Wasting Disorders introduced a generic definition for all types of cachexia: "a complex metabolic syndrome associated with underlying illness characterized by loss muscle, or without fat loss". It is well-known that presence inflammatory burden in end-stage renal disease (ESRD) patients may lead to evolution cachexia. Since etiology cachexia chronic kidney (CKD) multifactorial, thus successful treatment must involve several concomitant measures (nutritional interventions, appetite stimulants, anti-inflammatory pharmacologic agents) provide integrated effective therapeutic modalities combat causative factors alleviate outcomes patients. Given high mortality rate cachexia, developing new are prerequisite ameliorating CKD worldwide. The present review aims discuss some strategies an update advances nutritional approaches counteract

Язык: Английский

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Bone mineral density and mortality in end-stage renal disease patients

Clinical Kidney Journal, Год журнала: 2020, Номер 13(3), С. 307 - 321

Опубликована: Апрель 28, 2020

Abstract Osteoporosis characterized by low bone mineral density (BMD) as assessed dual-energy X-ray absorptiometry (DXA) is common among end-stage renal disease (ESRD) patients and associates with high fracture incidence all-cause mortality. This because chronic kidney disease-mineral disorders (CKD-MBDs) promote not only (osteoporosis dystrophy) but also vascular calcification cardiovascular disease. The disturbed metabolism in ESRD leads to ‘loss of cortical bone’ increased porosity thinning rather than loss trabecular bone. Low BMD, especially at cortical-rich sites, closely linked CKD-MBD, poor outcomes. These effects appear be largely mediated shared mechanistic pathways via the ‘bone–vascular axis’ through which impaired status changes wall. Thus, more just scaffolding that holds body together protects organs from external forces is—in addition its physical supportive function—also an active endocrine organ interacts vasculature paracrine factors including Wnt signalling, osteoprotegerin (OPG)/receptor activator nuclear factor-κB (RANK)/RANK ligand system Galectin-3/receptor advanced glycation end products axis. insight osteogenesis share many similarities—and knowledge a cell-mediated passive mineralization process—suggest BMD (‘vascular ossification’) large extent represent two sides same coin. Here, we briefly review observed using different DXA methods (central whole-body DXA) sites for measurements, summarize recent regarding relationships between ‘low BMD’ ‘fracture incidence, mortality’ patients, well potential ‘molecular mechanisms’ underlying these associations.

Язык: Английский

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