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[Mechanism research of imperatorin in combination with long-wave ultraviolet in inducing cellular senescence through regulating GADD45A/Cyclin B1/CDK1 axis].

This study aims to investigate the phototoxic effects of imperatorin(IMO) and its potential mechanisms of inducing skin photodamage and cellular senescence. A phototoxicity model was established on the dorsal skin of SD rats, which were randomly divided into a control group, an IMO group(0.8 mg·cm~(-2)), a long-wave ultraviolet A(UVA) group(10 J·cm~(-2)), and an IMO + UVA group. The rats were continuously observed for 72 h, and Draize skin scores were assessed. Hematoxylin-eosin(HE) staining was used to observe histopathological changes, and Verhoeff-Van Gieson(VVG) staining was utilized to ev…

YTH N6-methyladenosine RNA binding protein 2 mediated m6A modification of circHIPK2 promotes cellular senescence and osteoarthritis progression by inhibiting autophagy.

N6-methyladenosine (m6A) modification has emerged as a critical post-transcriptional regulatory mechanism in osteoarthritis (OA). However, the contribution of m6A-dependent regulation of circular RNAs (circRNAs) to chondrocyte senescence and OA progression remains poorly understood. We aimed to elucidate whether m6A-mediated control of circRNAs regulates chondrocyte senescence and to define the underlying molecular mechanisms contributing to OA progression. Here, we identified an OA-associated circRNA, circHIPK2, and demonstrated that its abundance and function are regulated by an m6A reader-d

Investigating the causal role of cellular senescence-related genes in preeclampsia: a multi-omics Mendelian randomization study with differential expression analysis.

BACKGROUND: The causal role of cellular senescence in preeclampsia pathogenesis is not fully established. This study aimed to systematically prioritize key senescence-related genes potentially driving preeclampsia using a Mendelian randomization (MR) framework. RESULTS: We integrated genome-wide association studies (GWAS) of preeclampsia with expression, methylation, and proteomic quantitative trait loci (eQTLs/mQTLs/pQTLs) data for 866 senescence-related genes. Summary-data-based MR (SMR) coupled with the HEIDI (Heterogeneity in Dependent Instruments) test were used to assess causal associat…

Loganin, an Iridoid Glycoside, Alleviates Paclitaxel-Induced Skeletal Muscle Toxicity by Enhancing Mitochondrial Function, Boosting Antioxidant Defenses, and Reducing Cellular Senescence.

Mitochondrial dysfunction and energy imbalance caused by chemotherapy are key contributors to skeletal muscle atrophy, which severely impacts the quality of life in cancer patients. Paclitaxel, a commonly used chemotherapeutic agent, is known to promote muscle wasting and cellular senescence, largely by impairing mitochondrial function. In this study, we investigated the protective role of loganin, a naturally occurring iridoid glycoside, in preventing paclitaxel-induced damage to skeletal muscle cells. Using C2C12 cells, we assessed whether loganin could counteract the harmful effects of pacl…

Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a pro-fibrotic and pro-tumorigenic inflammatory microenvironment.

BACKGROUND AND AIMS: RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a r … tosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51fl/fl ; Alb -Cre +/+ mice. While liver regeneration is compromised in Rad51 -CKO mice, they are more tolerant of carbon tetrachloride-induced hepatic injury and resistan …

A novel anti-HBV agent, E-CFCP, restores Hepatitis B virus (HBV)-induced senescence-associated cellular marker perturbation in human hepatocytes.

Cellular senescence is a cellular state with a broad spectrum of age-related physiological conditions that can be affected by various infectious diseases and treatments. Therapy of hepatitis B virus (HBV) infection with nucleos(t)ide analogs [NA(s)] is well established and benefits many HBV-infected patients, but requires long-term, perhaps lifelong, medication. In addition to the effects of HBV infection, the effects of NA administration on hepatocellular senescence are still unclear. This study investigated how HBV infection and NA treatment influence cellular senescence in human hepatocytes…

The protective effects of etomidate against interleukin-1β (IL-1β)-induced oxidative stress, extracellular matrix alteration and cellular senescence in chondrocytes.

Osteoarthritis (OA) is a common chronic inflammatory disease associated with aging. Etomidate is an intravenous anesthetic with profound ant … t etomidate protected C28/I2 chondrocytes from IL-1β-induced oxidative stress, ECM degradation, and cellular senescence via activating AMPK signaling.

Delivery of Sonic Hedgehog Gene Repressed Irradiation-induced Cellular Senescence in Salivary Glands by Promoting DNA Repair and Reducing Oxidative Stress.

Rationale: Irreversible hypofunction of salivary glands or xerostomia is common in head and neck cancer survivors treated with radiotherapy … l GFP gene into submandibular glands (SMGs) via retrograde ductal instillation 3 days after IR. The cellular senescence was evaluated by senescence-associated beta-galactosidase assay and the expression of senescence markers. The underlying mechanisms were explored by examining DNA damage, oxidative stress, and the expression of related genes by qRT-PCR, Western blot …

Induction of cellular senescence in a telomerase negative human immortal fibroblast cell line, LCS-AF.1-3, by human chromosome 6.

In immortal cells (LCS-AF.1-3) which originated from cultured skin fibroblasts from a patient with Li-Fraumeni syndrome, a specific deletion has been identified on chromosome 6. To examine the relationship between this deletion and the loss of function in aging genes, we performed microcell mediated chromosome transfer (MMCT) of normal human chromosome 6 into LCS-AF.1-3 cells and analyzed their characteristics. Transferred human chromosome 6 induced morphological changes in the cells and cellular senescence with growth suppression. In a revertant clone that had escaped from induced senescence,…

Protective effect of Florfenicol against DSS-induced ulcerative colitis by inhibiting cellular senescence and reducing inflammation via the AMPK signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory disorder of unclear etiology. Senescence-related signs have been detected in the intestina … nd colon tissue senescence. Interestingly, we found that FLO can effectively counteract DSS-induced cellular senescence and alleviate DSS-induced ulcerative colitis and colon senescence in C57BL/6j mice. Moreover, we provide strong evidence that FLO effectively inhibits colon senescence and treats DSS-induced colitis by activating the AMPK signaling pathway. Conseque …

Total flavonoids of litchi seed attenuates cellular senescence by inhibiting the production of SASP through p65 suppression and ameliorates pulmonary fibrosis.

Anti-aging foods not only benefit elderly individuals but also drive the development of safe and effective natural drugs. Here, we report th … anistically, TFL suppresses p65 protein expression, thereby inhibiting IL-1α and IL-1β and delaying cellular senescence. Gut microbiome analysis reveals that the abundance and functions of the mouse gut microbiome change after BLM exposure and that TFL treatment reverses these changes. Overall, we provide a theoretical basis for the future application of TFL as a pot …

Multi-Omics and Machine Learning-Uncovered FLT1-Mediated Epithelial-Endothelial Crosstalk in Cellular Senescence Driving Clear Cell Renal Cell Carcinoma Malignancy.

Clear cell renal cell carcinoma (ccRCC) is distinguished by the absence of definitive diagnostic markers and efficacious treatment modalities, factors that collectively contribute to its unfavorable clinical prognosis. The targeting of senescent cells has recently emerged as a promising therapeutic strategy. Nevertheless, the precise role of cellular senescence in the pathophysiology of ccRCC has yet to be comprehensively elucidated. This study sought to investigate the role of cellular senescence levels in ccRCC through comprehensive transcriptomic, proteomic, spatial transcriptomic, and sing…

Therapy-Induced Cellular Senescence in Non-Hodgkin Lymphomas, with Emphasis on Aggressive B-Cell Subtypes: Molecular Mechanisms and Emerging Drug Targets.

INTRODUCTION/BACKGROUND: Therapy-Induced Senescence (TIS) is increasingly recognized as a clinically relevant outcome of anticancer therapy, … MEDLINE, Scopus, and Google Scholar using combinations of the terms "therapy-induced senescence", "cellular senescence", "SASP", "senolytic", "senomorphic", and "senescence escape". Priority was given to studies published between 2010 and 2026, while older land-mark studies were included when mechanistically essential. RESULTS: TIS is initiated by persistent DDR si …

The cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts.

Ataxia-telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of the homeostatic protein kinase ATM. The complex phenotype of A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts from A-T patients exhibit premature senescence, highlighting the association between genome instability, cellular senescence, and aging. We found that lung fibroblasts derived fro…

P18 SKIN EXPRESSION OF P16INK4A, A BIOMARKER FOR CELLULAR SENESCENCE, DOES NOT PREDICT FRAILTY OR TREATMENT OUTCOME IN NEWLY DIAGNOSED MULTIPLE MYELOMA

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… The cell cycle regulator and tumor suppressor p16 INK4a has been found to be a robust biomarker of cellular senescence and aging. … Recent literature suggests that p16 INK4a mRNA expression in peripheral T cells could be a more accurate marker for cellular senescence. …

Cellular senescence in kidney biopsies is associated with tubular dysfunction and predicts CKD progression in childhood cancer patients with karyomegalic interstitial nephropathy.

Karyomegalic interstitial nephropathy (KIN) has been reported as an incidental finding in patients with childhood cancer treated with ifosfamide. It is defined by the presence of tubular epithelial cells (TECs) with enlarged, irregular, and hyperchromatic nuclei. Cellular senescence has been proposed to be involved in kidney fibrosis in hereditary KIN patients. We report that KIN could be diagnosed 7-32 months after childhood cancer diagnosis in 6/6 consecutive patients biopsied for progressive chronic kidney disease (CKD) of unknown cause between 2018 and 2021. The morphometry of nuclear size…

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning.

Recurrent implantation failure (RIF) is an extremely thorny issue in in-vitro fertilization (IVF)-embryo transfer (ET). However, its intricate etiology and pathological mechanisms are still unclear. Nowadays, there has been extensive interest in cellular senescence in RIF, and its involvement in endometrial immune characteristics during the window of implantation (WOI) has captured scholars' growing concerns. Therefore, this study aims to probe into the pathological mechanism of RIF from cellular senescence and investigate the correlation between cellular senescence and endometrial immune char…

Taurine ameliorates cellular senescence associated with an increased hydrogen sulfide and a decreased hepatokine, IGFBP-1, in CCl4-induced hepatotoxicity in mice.

This study investigated the protective effects of taurine against cellular senescence and hepatokine secretion in a mouse model of carbon tetrachloride (CCl4)-induced chronic liver injury. Oral taurine administration by tap water containing 3 % taurine significantly attenuated liver damage, as evidenced by reduced serum AST, ALT level and hepatic lipid peroxidation. Importantly, hepatic taurine level is reduced in CCl4-induced injury model, while taurine administration recovered it. Moreover, taurine administration decreased the numbers of p21-positive senescent cells in liver tissue of CCl4-t…

Modulation of cellular senescence in psoriatic arthritis: exploring the potential impact of bDMARDs on telomere length, mtDNA copy number, and oxidative damage.

Inflammation and cellular senescence are two interconnected biological processes critical for several chronic diseases. Pro-inflammatory factors promote the accumulation of reactive oxygen species, which synergistically accelerate the deterioration process. This creates a feedback loop that exacerbates telomere attrition and mitochondrial dysfunction, hallmarks of cellular senescence. Conventional therapies have been shown to influence oxidative stress and consequently cellular senescence, while the impact of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) is…

Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint.

Rheumatoid arthritis (RA) is a chronic systemic and autoimmune disease that primarily affects joints and causes pain, stiffness and swelling. The affected joints exhibit severe inflammation in the synovium and bone erosion, leading to joint deformity. Aging is an important factor facilitating the development of RA, as it is associated with an increase in the number of senescent cells and the production of the autoantibodies and proinflammatory cytokines in tissues. Given that CCN3 is highly expressed in RA joints and that its level is associated with the severity of the disease, we explored it