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Prognostic impact of a senescence gene signature in multiple myeloma.

Multiple myeloma (MM), an incurable malignancy of plasma cells, is predominantly an age-related disease, with the majority of cases occurring in patients over the age of 60. Cellular senescence, a fundamental biological process underlying aging, has been increasingly recognized for its critical role in developing age-related malignancies. In this study, we aimed to investigate the prognostic significance of genes implicated in the molecular mechanisms of senescence within a large cohort of MM patients. Gene expression and clinical data from 1416 MM patients were obtained from four GEO datasets…

Progressive fibrosis in human MASLD is associated with spatially linked transcriptomic signatures of metabolic reprogramming and senescence.

BACKGROUND & AIMS: Granular detail about the location and nature of liver cell interactions and the metabolic, inflammatory and fibrogenic pathways driving progressive fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) is needed to identify novel therapeutic targets. METHODS: We generated Visium spatial transcriptomic data from 33 human liver biopsies across the spectrum of MASLD. Gene expression data were overlaid with histological annotations to integrate spatial molecular and histopathological information, enabling interrogation of disease progression. Differentia

Targeting DDR1 with novel synthesized antagonists delays cellular aging and enhances wound healing in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are central to regenerative medicine; however, their clinical utility is constrained by reduced proliferative capacity and replicative senescence during ex vivo expansion. Here, we report on the rational design and biological characterization of novel phthalimide-based inhibitors targeting discoidin domain receptor 1 (DDR1). Structure-activity relationship optimization efforts led to the identification of AC-4067 and AC-4061 as potent DDR1 inhibitors, with IC₅₀ values of 30.9 nM and 53.6 nM, respectively. AC-4067 demonstrated 18-fold selectivity for DDR1 over DDR2

Clinical translation of senescence-related pan-cancer multi-omics: tools for assessment and immunotherapy prediction.

Cellular senescence (CS) exerts dual roles in tumorigenesis, yet its pan-cancer molecular characteristics and clinical value remain unclear, hindering its translation to oncology and personalized therapy. To address the lack of specific and universal tools for senescence assessment and immunotherapy response prediction, this study systematically analyzed 1259 CS-related genes from the CellAge database across 31 cancer types by integrating multi-omics data, including bulk RNA-seq, single-cell/spatial transcriptomics, and CRISPR screening. We developed a rank-based algorithm SenScoreR (publicly …

Renovascular Disease Induces Senescence in Renal Scattered Tubular-Like Cells and Impairs Their Reparative Potency.

Scattered tubular-like cells (STCs), dedifferentiated renal tubular epithelial cells, contribute to renal self-healing, but severe injury mi … uce senescence in endogenous STC and impair their reparative capacity. These observations implicate cellular senescence in the pathophysiology of ischemic kidney disease and support senolytic therapy to permit self-healing of senescent kidneys.

Вербовка подстрекательских моноцитов фибробластами для лиц пожилого возраста препятствует иммунитету антигенных тканей во время старения человека.

Ранее мы показали, что здоровые пожилые люди демонстрируют сокращение иммунной реакции во время антигенного заболевания вирусом варицелла (VZV), который соотносится с неспециальным подстрекательским реагированием на саму инъекцию. Здесь мы обнаружили, что повреждение иглы во время внутридермальных инъекций у пожилых людей привело к увеличению числа резиновых фибробатров, выражающих CCL2, что привело к местной вербовке подстрекательских моноцитов. Эти инфильтрирующие моноциты секретировали простагландин Е2, который препятствовал активации и распространению локальной памяти T клеток. Предварител

Совпадение в аннотации оригинала
We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen … challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellular senescence, tissue damage, excessive inflammation and reduced immune responsiveness in human skin and demonstrate that tissue-specific immunity can be restored in older adults by short-term inhibition of inflammatory responses.

A taxifolin-zinc nanozyme with SOD-like activity attenuates oxidative-stress-induced senescence and extends lifespan in C. elegans.

Oxidative stress is a key driver of cellular senescence and functional decline. However, many natural polyphenols have limited bioavailability because they are difficult to formulate into stable systems. Here, we report a polyphenol-metal coordination nanozyme prepared by coordinating zinc with taxifolin and using L-arginine to regulate assembly. The resulting Tax-Zn nanozyme formed a well-dispersed nanoscale system with an average hydrodynamic diameter of 57.53 nm. Functionally, the nanozyme exhibited broad antioxidant capacity in several assays and showed slightly stronger activity than Tax …

Metabolic reprogramming in cancer and senescence.

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being the aging of the global population. … enescence and tumor metabolic reprogramming; as well as reveal the impact of key factors leading to cellular senescence on tumorigenesis. In addition, this review summarizes the current intervention strategies targeting nutrient sensing pathways, as well as the clinical cases of treating tumors targeting the characteristics of senescence with the existing nanodeliver …

cGAS-STING are responsible for premature aging of telomerase-deficient zebrafish.

Telomere shortening occurs in multiple tissues throughout aging. When telomeres become critically short, they trigger DNA-damage responses and p53 stabilization, leading to apoptosis or replicative senescence. In vitro, cells with short telomeres activate the cGAS-STING innate immune pathway resulting in type-I interferon-based inflammation and senescence. However, the consequences of these events for the organism are not yet understood. Here, we show that sting is responsible for premature aging of telomerase-deficient zebrafish. We generated sting-/- tert-/- double-mutant animals and observe

n-3 polyunsaturated fatty acids delay intervertebral disc degeneration by inhibiting nuclear receptor coactivator 4-mediated iron overload.

n-3 polyunsaturated fatty acids (PUFAs) are closely related to the progression of numerous chronic inflammatory diseases, but the role of n-3 PUFAs in the intervertebral disc degeneration (IVDD) remains unclear. In this study, male C57BL/6 wildtype mice (WT group, n = 30) and fat-1 transgenic mice (TG group, n = 30) were randomly selected to construct the IVDD model. The results demonstrated that the optimized composition of PUFAs in the TG mice had a significant impact on delaying IVDD and cellular senescence of intervertebral disc (IVD). Mechanismly, n-3 PUFAs inhibited IVD senescence by all…

Deciphering aging at three-dimensional genomic resolution.

Aging is characterized by progressive functional declines at the organismal, organic, and cellular levels and increased susceptibility to aging-related diseases. Epigenetic alteration is a hallmark of aging, senescent cells show epigenomic changes at multiple scales, such as 3D genome reorganization, alterations of histone modifications and chromatin accessibility, and DNA hypomethylation. Chromosome conformation capture (3C)-based technologies have enabled the generation of key information on genomic reorganizations during senescence. A comprehensive understanding of epigenomic alterations du

Osteocyte lacunar and cellular characteristics in the subchondral bone plate and trabecular bone of human knee osteoarthritis.

BACKGROUND: Subchondral bone (SB) plays a critical role in the development of osteoarthritis (OA), yet the structural and cellular organisation of osteocytes within subchondral compartments remains poorly characterised. This study investigated osteocyte lacunar morphology and cellular characteristics in human knee OA. METHODS: 16 osteochondral biopsies were obtained from nine patients undergoing primary knee arthroplasty for end-stage OA. Synchrotron radiation micro-computed tomography was used to quantify attenuation-based relative mineral density (RMD) and osteocyte lacunar morphometry with

ERG Orchestrates a Dedifferentiation-Senescence-Inflammation Triad in Prostate Cancer.

UNLABELLED: ERG fusions occur in about 50% of prostate cancers and represent early somatic events that co-initiate tumorigenesis. Yet, the molecular programs unleashed by ERG at disease onset remain elusive. In this study, the inducible, temporally controlled expression of ERG enabled the accurate mapping of early ERG-driven processes associated with an apparent decrease in cell fitness across a panel of prostate cells. We observed that ERG triggers senescence and epithelial-mesenchymal transition (EMT), generating distinct cellular states in which EMT and senescence coexist in the same cell o

Mitigating nucleus pulposus cell senescence in intervertebral disk degeneration: the role of nodakenin in SIRT6 and PINK1/Parkin-associated mitophagy signaling.

Intervertebral disc degeneration (IVDD) is a common and challenging chronic condition in orthopedics, primarily characterized by the aging of nucleus pulposus cells (NPC). Current treatment strategies for IVDD, particularly those targeting NPC senescence, remain underdeveloped. Research has shown that NPC senescence is closely associated with mitochondrial damage, leading to the accumulation of cytoplasmic reactive oxygen species (ROS) and mitochondrial DNA (mtDNA). Mitochondrial autophagy, as a key mechanism of mitochondrial quality control, regulates ROS and mtDNA levels by eliminating dysfu

Identification of senescence related hub genes and potential therapeutic compounds for dilated cardiomyopathy via comprehensive transcriptome analysis.

BACKGROUND: Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, the role of cellular senescence in DCM has not been fully elucidated. Here, we aimed to investigate senescence in DCM, identify senescence related characteristic genes, and explore the potential small molecule compounds for DCM treatment. METHODS: DCM-associated datasets and senescence-related genes were respectively obtained from Gene Expression Omnibus (GEO) database and CellAge database. The characteristic genes were identified through methods including weighted gene co-expression network analysis (WGCNA)…

Downregulation of Pin1 in human atherosclerosis and its association with vascular smooth muscle cell senescence.

OBJECTIVE: Pin1 is prevalently overexpressed in human cancers and implicated to regulate cell growth and apoptosis. Thus far, however, no ro … SMCs, synchronously with increased VSMC senescence. Adenoviral-mediated Pin1 overexpression rescued cellular senescence in atherosclerotic VSMCs, with concurrent down-regulation of P53, p21, growth arrest and DNA-damage-inducible protein 45-alpha (Gadd45a), phosphorylated retinoblastoma (p-pRb), p65 and upregulation of cyclin subfamilies (cyclin B, D, and E), and cyc …

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by unknown causes and a poor prognosis. Recent research indicates that age-related mechanisms, such as cellular senescence, may play a role in the development of this condition. However, the relationship between cellular senescence and clinical outcomes in IPF remains uncertain. METHODS: Data from the GSE70867 database were meticulously analyzed in this study. The research employed differential expression analysis, as well as univariate and multivariate Cox regression analysis, to pinpoint sen…

Autofluorescence and cell size-based sorting eliminates senescent cells in synovial mesenchymal stem cells from patients with osteoarthritis.

INTRODUCTION: The presence of senescent cells in synovial mesenchymal stem cell (MSC) preparations reduces the therapeutic efficacy of MSCs … logy, and senescence-associated β-galactosidase (SA-β-gal) activity were evaluated as indicators of cellular senescence, and colony-forming ability and trilineage differentiation potentials (adipogenesis, osteogenesis, and chondrogenesis) were assessed as indicators of stem cell function. RESULTS: The AFlowFSClow fraction had a smaller cell diameter, less enlarged a …

The chemotherapeutic drug doxorubicin does not exacerbate p16Ink4a-positive senescent cell accumulation and cardiometabolic disease development in young adult female LDLR-deficient mice.

Cancer survivors who received chemotherapy, such as the anthracycline doxorubicin (DOX), have an increased risk of developing complications later in life, including the development of chronic metabolic diseases. Although the etiology of this increased risk for late metabolic complications in cancer survivors is poorly understood, a causal role of therapy-induced senescent cells has been suggested. To study the role of cellular senescence in chemotherapy-induced metabolic complications, young adult female low-density lipoprotein receptor-deficient (Ldlr-/-)-p16-3MR mice, in which p16Ink4a-posit…

The lncRNA, H19 Mediates the Protective Effect of Hypoxia Postconditioning Against Hypoxia-Reoxygenation Injury to Senescent Cardiomyocytes by Targeting microRNA-29b-3p.

BACKGROUND: Ischemic postconditioning (I/Post) is an endogenous protection mechanism that reduces injury induced by ischemia-reperfusion (I/R). It remains controversial whether I/Post protects against I/R injury to the aging heart. The long non-coding RNA, H19 protects H9c2 cells against hypoxia-induced injury. This study aimed to elucidate the role of H19 in the hypoxic postconditioning (H/Post) of aged cardiomyocytes. METHODS: Senescence induced by D-galactose in primary cardiomyocytes from neonatal Sprague-Dawley rats was measured by senescence-associated β-galactosidase staining. Hypoxic