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Preserving joint healthspan in knee osteoarthritis: a geroscience-guided review of non-surgical therapies and genicular artery embolization.

Knee osteoarthritis (KOA) is a leading cause of late-life pain, mobility loss, and disability, and is increasingly recognized as a phenotype-dependent manifestation of joint aging rather than a purely mechanical disorder. Cellular senescence, inflammaging, mitochondrial dysfunction, synovial inflammation, vascular remodeling, and impaired repair capacity converge to shape KOA symptoms and progression. This narrative review synthesizes evidence on conservative and minimally invasive KOA therapies within a geroscience-guided, phenotype-informed framework. A structured search of PubMed/MEDLINE an…

Microfluidic Mechanical Reactivation of Senescent Stem Cells.

Stem cell aging significantly impairs therapeutic efficacy, requiring innovative strategies to restore potency. We present a microfluidic cell-compressing platform for reactivation (µ-CPR) designed to apply controlled hydrodynamic deformation to late-passage stem cells. This mechanical stimulation facilitates functional reactivation without external chemical cues. Within a defined window, µ-CPR reduces oxidative stress, SA-β-gal activity, and γ-H2A.X foci, while enhancing proliferation and increasing the expression of canonical stemness-associated markers, including OCT4, SOX2, and KLF4. Mecha

Attenuating monocytic inflammaging via the miR-146a/TLR4 axis: Characterization and bioactivity of a triterpenoid-rich callus phytocomplex.

Inflammaging, driven by monocyte dysregulation, is a hallmark of immunosenescence. Toll-like Receptor 4 (TLR4) pathway hyper-activation accelerates cellular senescence and systemic inflammatory damage, while microRNA-146a (miR-146a) constrains pro-inflammatory cytokine release by targeting IRAK-1. Plant-derived triterpenoids are promising geroprotective agents, but standardized, scalable biotechnological production remains challenging. We established a sustainable in vitro callus culture from Red Sentinel to obtain a standardized triterpenoid-rich extract (RSE). GC-MS/FID analysis quantified i…

Protocol for the REBOUND study: a cohort study to uncover fundamental mechanisms of accelerated ageing and impaired resilience following cancer surgery and treatment.

BACKGROUND: Ageing is a heterogeneous process, which is associated with heterogeneous resilience in older people. Cancer surgery and treatme … points to measure underlying hallmarks of ageing including inflammation, dysbiosis, macroautophagy, cellular senescence, epigenetic alterations, mitochondrial dysfunction, and stem cell exhaustion. A machine learning approach will be utilised to evaluate the associations between trajectories in clinical and physiological parameters and fundamental biological processe …

Inhibiting Cyclin-Dependent Kinase 13-Mediated Nuclear Ubiquitous Casein Kinase and Cyclin-Dependent Kinase Substrate 1 Phosphorylation Facilitates Oxidative Stress-Induced Apoptosis in Melanoma.

Cellular responses after oxidative stress-induced deoxyribonucleic acid (DNA) damage (e.g., DNA double-strand break) control tumor cell proliferation, senescence, and apoptosis. The nuclear ubiquitous casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) ensures replication feasibility by modulating double-strand break repair necessary to regulate tumor cell proliferation. However, the regulatory mechanism of NUCKS1 in oxidative stress-induced melanoma cell apoptosis is not well characterized. In this study, we reported reduced phosphorylation of NUCKS1 during oxidative stress-mediate

The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.

Bone tumors, encompassing heterogeneous primary and metastatic lesions, are driven in their initiation, progression, and metastasis by dysregulation of the bone microenvironment (BME). Clinically manifested by localized pain, pathological fractures, and neurological deficits, these malignancies substantially threaten patient survival. Radiographic patterns (osteolytic, osteoblastic, mixed) directly reflect pathogenic BME-tumor interactions, particularly involving osteoblast-osteoclast imbalance. The BME-a specialized niche of bone-resident cells (osteocytes, osteoblasts, osteoclasts), immune c

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… Regulatory mechanisms of senescent microenvironment in bone tumor and metastasis Aging—the inevitable progression toward death observed in most living organisms—manifests at the cellular level (life's fundamental unit) as cellular senescence. … senescence as a pivotal driver of bone tumorigenesis. …

Naringenin boosts Parkin-mediated mitophagy via estrogen receptor alpha to maintain mitochondrial quality control and heal diabetic foot ulcer.

Diabetic foot ulcer (DFU) is an increasing global burden due to the rising prevalence of diabetes, and no specific pharmacological targets or satisfactory drugs are currently available for this devastating ailment. In this study, naringenin (NAR) was found to accelerate diabetic wound healing in diabetic C57BL/6J wild-type (WT) mice by reducing oxidative stress, as assessed through histological assay. NAR also alleviated the inhibition of proliferation, inflammation, cell senescence, and apoptosis in HaCaT cells induced by high glucose (HG). Mechanistically, the beneficial effects of NAR on wo

Profiling microRNA from peripheral blood mononuclear cells in early-onset familial Alzheimer's disease.

MicroRNAs (miRNAs) refer to short in-length, noncoding RNAs that regulate numerous cellular functions by targeting mRNA, and numerous types of research have shown that miRNA is vitalin Alzheimer's disease. For identifying differentially expressed miRNAs in the peripheral blood mononuclear cell (PBMC) of early-onset familial Alzheimer's disease (EOFAD), we conducted this study which might give a reference for potential therapeutic targets or biomarkers for this disease. On the basis of high-throughput sequencing, we screened the miRNAs expression profiles in PBMC regarding both EOFAD patients a

Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis.

Liver fibrosis and fibrosis-associated hepatocarcinogenesis are driven by chronic inflammation and are leading causes of morbidity and death … Further, hepatic expression of genes regulating angiogenesis, apoptosis, cell cycle regulation, and cellular senescence were affected by targeting SYK. We found that SYK inhibition mitigated both HSC trans-differentiation and acquisition of an inflammatory phenotype in T cells, B cells, and myeloid cells. However, in vivo experiments employing selective targeted dele …

Salivary gland regeneration: from salivary gland stem cells to three-dimensional bioprinting.

Hyposalivation and severe dry mouth syndrome are the most common complications in patients with head and neck cancer (HNC) after receiving radiation therapy. Conventional treatment for hyposalivation relies on the use of sialogogues such as pilocarpine; however, their efficacy is constrained by the limited number of remnant acinar cells after radiation. After radiotherapy, the salivary gland (SG) secretory parenchyma is largely destroyed, and due to the reduced stem cell niche, this gland has poor regenerative potential. To tackle this, researchers must be able to generate highly complex cellu

Skewed T cell responses to Epstein-Barr virus in long-term asymptomatic kidney transplant recipients.

Kidney transplant recipients (KTRs) abnormally replicate the Epstein Barr Virus (EBV). To better understand how long-term immunosuppression impacts the immune control of this EBV re-emergence, we systematically compared 10 clinically stable KTRs to 30 healthy controls (HCs). The EBV-specific T cell responses were determined in both groups by multiparameter flow cytometry with intra cellular cytokine staining (KTRs n = 10; HCs n = 15) and ELISpot-IFNγ assays (KTRs n = 7; HCs n = 7). The T/B/NK cell counts (KTRs n = 10; HCs n = 30) and the NK/T cell differentiation and activation phenotypes (KTR

A clinical approach to brown adipose tissue in the para-aortic area of the human thorax.

BACKGROUND: Human thoracic brown adipose tissue (BAT), composed of several subdivisions, is a well-known target organ of many clinical studies; however, the functional contribution of each part of human thoracic BAT remains unknown. The present study analyzed the significance of each part of human thoracic BAT in the association between regional distribution, cellularity, and factors involved in the functional regulation of thoracic BAT. METHODS: We analyzed 1550 healthy adults who underwent medical check-ups by positron-emission tomography and computed tomography (PET-CT) imaging, 8 cadavers

Oxygen radical detoxification processes during aging: the functional importance of melatonin.

That free radical destruction of macromolecules is a basis of aging and age-related diseases has considerable experimental support. Melatonin, a hormone produced in organisms as diverse as algae and humans, is believed to have evolved coincident with aerobic metabolism. In all organisms melatonin is produced primarily during the daily period of darkness, with only small amounts being synthesized during the day. In mammals including man, melatonin is produced by and secreted from the pineal gland during the night; however, the night-time production of melatonin falls markedly with aging such th

ZNF384-Driven Fibulin-1 Exacerbates Vascular Stiffness via TGF-β/Smad3-Mediated Senescence and Fibrosis.

Vascular stiffness, a hallmark of aging and cardiovascular disease, involves vascular smooth muscle cell (VSMC) senescence and extracellular matrix (ECM) dysregulation. This study investigates the role of fibulin-1 (Fbln1) in these processes. Plasma proteomic profiling identified dysregulated proteins in vascular stiffness pedigrees. Fbln1 knockout mice and dual vascular stiffness models (natural aging and chronic angiotensin II [Ang II] infusion) were established. Phenotypic assessments included pulse wave velocity (PWV), histology, and molecular markers. Mechanistic investigations integratin

CXCR2 affects sensitization of radioresistant HPV-negative head and neck squamous cell carcinoma cells by ABT-263.

BACKGROUND: Radiation-induced senescence strongly contributes to therapy resistance in HPV-negative head and neck squamous cell carcinoma (HNSCC). In particular, the NF-[Formula: see text]B-dependent arm of the senescence-associated secretory phenotype (SASP) activates signaling pathways that are tightly associated with, and promote, resistance to irradiation. In addition to the SASP, another hallmark of senescence is the upregulation of anti-apoptotic proteins. The BH3-only mimetic ABT-263 has been shown to effectively eliminate senescent cells. In this study, we employed ABT-263 to overcome

Targeting MYCN Degradation by HLB-0532259 Induces Senescence in Retinoblastoma.

PURPOSE: Amplification of MYCN is a primary driver of aggressive retinoblastoma (RB), yet it remains a challenging therapeutic target. This study aimed to evaluate the therapeutic potential of the PROTAC molecule HLB-0532259 in degrading MYCN and suppressing RB growth. METHODS: Y79 and WERI-Rb1 RB cell lines were treated with HLB-0532259, and MYCN protein degradation, cell viability, and time-dependent transcriptional changes were assessed by Western blotting, cell viability assays, RNA-seq, and proteomics. The therapeutic potential was further validated in an orthotopic Y79 xenograft mouse m

(Pro)renin receptor promotes cardiomyocyte senescence via tripartite motif-containing 24-mediated stabilization of p53 in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and a leading contributor to heart failure, in which cardiomyocyte senescence plays an increasingly recognized role. However, the underlying mechanisms driving this process remain poorly defined. Here, we identify the (pro)renin receptor (PRR) as a critical mediator of cardiomyocyte senescence in DCM. Using a high-fat diet and streptozotocin (STZ)-induced DCM mouse model, as well as primary cardiomyocytes exposed to high glucose and palmitic acid, we demonstrate that PRR expression is significantly upregulated in diabetic hearts

IRF8 and RUNX1 cooperatively regulate the senescence and damage of urine-derived renal progenitor cells by upregulating LINC01806.

Urine-derived renal progenitor cells (UdRPCs) from healthy individuals have been identified as having the potential to repair kidney damage. However, it remains uncertain whether UdRPCs retain their functionality in chronic kidney disease (CKD) patients. In this study, UdRPCs were isolated from healthy individuals and CKD patients. Notably, senescent cells were observed in the UdRPCs of CKD patients, which increase with the severity of CKD, hindering the repair of renal tissue damage and exacerbating the progression of CKD. This senescence phenotype is characterized by decreased proliferation,

Transcription factor MEOX1 accelerates pulmonary fibrosis by regulating mitophagy and senescence.

Idiopathic pulmonary fibrosis (IPF) is a kind of chronic and progressive interstitial lung disease of unclear aetiology. A key aspect of IPF is transforming growth factor-β1 (TGF-β1)-induced mitophagy dysfunction and senescence in lung fibroblasts. Mesenchyme homeobox 1 (MEOX1) is a critical transcription factor in the regulation of cell differentiation. However, the role of MEOX1 in the pathogenesis of lung fibrosis and mitophagy has not been clarified. In this study, RNA-sequencing analysis was employed to identify the differentially expressed genes in TGF-β1-treated lung fibroblasts and IPF

Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease.

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were mea