Результаты поиска

A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.

Liver aging is characterized by chronic inflammation and metabolic dysfunction that drive progression of metabolic dysfunction-associated st … mice (MLKLHepOE), we find that MLKL overexpression does not induce necroptosis but instead promotes cellular senescence, evidenced by increased p16INK4a and p21WAF1/Cip1 and elevated senescence associated secretory phenotype (SASP). Mechanistically, MLKL induces hepatocyte mitochondrial dysfunction, with impaired respiration, altered mitochondrial dynamics, and incre …

Rapamycin Inhibits Senescence and Improves Immunomodulatory Function of Mesenchymal Stem Cells Through IL-8 and TGF-β Signaling.

Mesenchymal stromal cells (MSCs) grown in high-density monolayers (sheets) are promising vehicles for numerous bioengineering applications. … via microarray analysis. Rapamycin significantly increased PMSC sheet autophagy activity, inhibited cellular senescence, decreased cell size and granularity at all timepoints. Rapamycin also significantly decreased the number of cells in late apoptosis at day 7 of sheet culture, as well as caspase 3/7 activity at all timepoints. Notably, while rapamycin decreased IL- …

Homocysteine accelerates senescence of endothelial cells via DNA hypomethylation of human telomerase reverse transcriptase.

OBJECTIVE: Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation … ith chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II-stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted t …

Identification of senescence-related genes in Parkinson's disease reveals candidate therapeutic targets and pathological processes.

BACKGROUND: Parkinson's disease (PD), a progressive neurodegenerative disease, is closely linked to the aging process; however, its precise … reduced tyrosine hydroxylase (TH) expression, promoted α-synuclein (α-syn) aggregation, aggravated cellular senescence, and caused significant upregulation of IRF7, whereas IRF7 small interfering RNA (siRNA) intervention reversed senescence- and PD-related pathological changes. Molecular docking analyses identified candidate small molecules targeting hub genes, incl …

[Jintiange Capsule alleviates glucocorticoid-induced osteoporosis in rats by inhibiting vascular endothelial cell senescence and promoting bone formation].

OBJECTIVES: To investigate the role of cellular senescence in glucocorticoid-induced osteoporosis and explore the therapeutic mechanism of Jintiange (JTG) Capsule. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) and mouse pre-osteoblasts (MC3T3) were treated with methylprednisolone (MPS) or MPS combined with JTG Capsule dissolved in saline. HUVEC senescence pathways and repair capacity were analyzed using Western blotting, SA-β-Gal staining, DCFH-DA assay, scratch wound healing, and RT-PCR. The osteogenic potential of MC3T3 cells was assessed using immunofluorescence stainin…

Necroptosis-senescence crosstalk in tubulointerstitial fibrosis: the mtDNA-cGAS-STING-PFKFB3 axis as a metabolic bridge.

BACKGROUND: Chronic kidney disease progresses irreversibly toward tubulointerstitial fibrosis. Although renin-angiotensin system inhibitors and sodium-glucose cotransporter 2 inhibitors slow progression, they cannot block or reverse fibrosis. Recent work shows that necroptosis and cellular senescence in tubular epithelial cells are not independent events; they form a dynamically evolving continuum through the mitochondrial DNA-cyclic GMP-AMP synthase-stimulator of interferon genes-interferon regulatory factor 3-6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3-glycolysis axis. METHODS: W…

KAT7 contributes to ponatinib-induced hypertension by promoting endothelial senescence and inflammatory responses through activating NF-κB signaling pathway.

BACKGROUND AND PURPOSE: Ponatinib, a tyrosine kinase inhibitor (TKI) leads to hypertension; however, the mechanisms remain elusive. We aimed to investigate whether lysine acetyltransferase 7 (KAT7), a key regulator of cellular senescence that is closely associated with cardiovascular diseases, involves in ponatinib-induced hypertension. METHODS AND RESULTS: After administering ponatinib to Sprague-Dawley (SD) rats for 8 days, we measured blood pressure, vasodilation, and endothelial function using tail-cuff plethysmography, isometric myography, and the Total NO Assay kit, respectively. The re…

Bioinformatics-based discovery of intervertebral disc degeneration biomarkers and immune-inflammatory infiltrates.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not w … mediated signaling pathways, and inflammatory responses, with the key signaling pathways engaged in cellular senescence, apoptosis, Th1 and Th2 cell differentiation, and Th17 cell differentiation. Immune cell infiltration research revealed that T cells, lymphocytes, B cells, and NK cells were decreased in IVDD patients while monocytes, neutrophils, and CD8 T cells we …

Cultured Human Foreskin as a Model System for Evaluating Ionizing Radiation-Induced Skin Injury.

PURPOSE: Precise molecular and cellular mechanisms of radiation-induced dermatitis are incompletely understood. Histone variant H2A.J is associated with cellular senescence and modulates senescence-associated secretory phenotype (SASP) after DNA-damaging insults, such as ionizing radiation (IR). Using ex vivo irradiated cultured foreskin, H2A.J was analyzed as a biomarker of radiation-induced senescence, potentially initiating the inflammatory cascade of radiation-induced skin injury. METHODS: Human foreskin explants were collected from young donors, irradiated ex vivo with 10 Gy, and culture…

Is there a role for senotherapeutics in the treatment of giant cell arteritis?

Giant cell arteritis (GCA) is a large-vessel vasculitis predominantly affecting individuals over 50 years, with a peak incidence between 70 and 80 years. Its pathogenesis involves complex immunological cascades triggered by vascular dendritic cell activation, recruitment of CD4⁺ T cells and monocytes, T helper lymphocyte polarization, and vascular remodeling driven by myofibroblasts and fibroblasts. Growing evidence implicates cellular senescence (particularly in vascular smooth muscle cells, fibroblasts, endothelial cells, and immune cells) in the pathophysiology of GCA. Senescent cells (SC) …

Micro- and nanoplastics alter electrophysiological brain patterns and reshape human neurodevelopmental trajectories.

Environmental microplastics and nanoplastics (MNPs) are emerging contaminants that accumulate in human tissues, including the brain, yet the … neurodevelopment, is unknown. Here, we show that exposure to environmentally relevant MNPs induces cellular senescence and innate immune transcriptional programs in human brain organoids. Using region-specific cortical organoids, we demonstrate that synthetic polystyrene (PS), polyethylene terephthalate (PET), low-density polyethylene (LDPE), and high-density polyet …

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence.

BACKGROUND: Acute renal failure due to crush syndrome is one of the leading causes of death in disasters. Ischemic Postconditioning (IPC) is … omarkers of inflammation, renal function, renal tubular injury, and muscular injury, apoptosis, and cellular senescence in kidney were detected. RESULTS: Six hours after decompression, the levels of Serum Creatine (SCr), Blood Urea Nitrogen (BUN), K+, and Interleukin-6 (IL-6) in IPC-1min and IPC-5min groups were lower than Control, with a statistically significant d …

An SSK1-loaded decellularized annulus fibrosus matrix-based PD hydrogel alleviates intervertebral disc degeneration through modulation of NF-κB signaling and ferroptosis.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major cause of low back pain and is closely associated with inflammatory activation, extracellular matrix (ECM) degradation, cellular senescence, and ferroptosis in nucleus pulposus cells (NPCs). In this study, we aimed to clarify the therapeutic effects and underlying mechanisms of SSK1 and to develop an injectable SSK1-loaded hydrogel for localized and sustained treatment of IDD. METHODS: An interleukin-1β (IL-1β)-induced NPC degeneration model was established to evaluate ECM metabolism, ferroptosis, senescence, and inflammatory signal…

Reciprocal Regulation between lncRNA ANRIL and p15 in Steroid-Induced Glaucoma.

Steroid-induced glaucoma (SIG) is the most common adverse steroid-related effect on the eyes. SIG patients can suffer from trabecular meshwork (TM) dysfunction, intraocular pressure (IOP) elevation, and irreversible vision loss. Previous studies have mainly focused on the role of extracellular matrix turnover in TM dysfunction; however, whether the cellular effects of TM cells are involved in the pathogenesis of SIG remains unclear. Here, we found that the induction of cellular senescence was associated with TM dysfunction, causing SIG in cultured cells and mouse models. Especially, we establi…

ROS-Responsive H2S Release Attenuates Renal Aging by Preserving Mitochondrial Function and Mitigating Oxidative Stress.

Cellular senescence is a durable state of cell-cycle arrest, and the progressive accumulation of senescent cells compromises tissue repair and promotes age-related functional decline. ROS drive oxidative stress when excessively produced or inadequately cleared, thereby inducing mitochondrial dysfunction that accelerates senescence. In this work, ROS-responsive branched reductive compound HS-N has been designed and synthesized, which serves as a dual-functional donor: effectively scavenges ROS and simultaneously releases H2S, thereby converting a toxic stimulus into a beneficial signal. Consist…

From antioxidant to senotherapeutic: Repurposing n-acetylcysteine to counteract senescence via the HuR pathway in human endothelial cells.

Cellular senescence plays a dual role in physiology and pathology. While it contributes to tumour suppression and tissue repair, its persistence promotes chronic inflammation, tissue dysfunction, and age-related diseases. Oxidative stress is a major driver of this process, and the RNA-binding protein HuR serves as a regulator by stabilizing transcripts encoding antioxidant and stress-response proteins. In this study, we established an in vitro model of replicative senescence using human umbilical vein endothelial cells (HUVECs) and investigated the potential anti-aging effects of N-acetylcyste…

Matrix Gla protein suppresses osteoblast senescence and promotes osteogenic differentiation by the PI3K-AKT signaling pathway.

Age-related bone loss in mice is associated with senescent cell accumulation and reduced bone formation by osteoblasts. Matrix Gla protein (MGP), secreted by osteoblasts, is pivotal in regulating the bone extracellular matrix mineralization. Previous research has demonstrated that Mgp null mice exhibit osteopenia and fractures, and ultimately die prematurely. To elucidate the mechanisms underlying MGP's role of MGP in bone metabolism, we generated osteoblast-specific Mgp knockout (Mgp cKO) mice by crossing Mgpfl/fl mice with Bglap-Cre mice. The study revealed that in 3-month-old Mgp cKO male m

Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated sec

Совпадение в полном тексте источника
… Methotrexate and gemcitabine induce genotoxic stress by blocking DNA synthesis, thereby inducing cellular senescence [ 138 , 139 ]. … Cellular senescence has been confirmed to be a key contributor to inflammaging in many age-related malignancies [ 268 , 269 ]. …

TNF-α promotes α-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis.

Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism of Parkinson's disease progression. Recent evidence sugges … factors, TNF-α had the most robust stimulatory activity. Treatment of neurons with TNF-α triggered cellular senescence, as shown by transcriptomic analyses demonstrating induction of senescence-associated genes and immunoanalysis of senescence phenotype marker proteins. Interestingly, secretion of α-synuclein was increased in senescent neurons, reflecting acquisitio …

Tubular cell senescence and expression of TGF-beta1 and p21(WAF1/CIP1) in tubulointerstitial fibrosis of aging rats.

Kidney aging has been recognized as a chronic process of compromised renal function and structural changes in the tubulointerstitium and glomerulus. Cell senescence is associated with alterations in cell structure and function, including expression of cytokines and structural and regulatory components of extracellular matrix proteins. In this investigation, we tested the hypothesis that senescent renal cells may accumulate in vivo with advancing age. We also evaluated the expression of transforming growth factor (TGF)-beta1 and p21WAF1/CIP1 in aging kidneys. Sprague-Dawley rats at the ages of