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Copper Metabolism-Related Cell Death in Kidney Diseases: Molecular Mechanisms, Disease-Specific Evidence, and Translational Implications.

Copper is essential for mitochondrial respiration, antioxidant defense, extracellular matrix maturation, and cellular signaling, yet disturbances in its abundance or intracellular distribution can damage the kidney through mechanistically distinct pathways. Cuproptosis is a specific copper-dependent form of regulated cell death in which copper binds lipoylated mitochondrial proteins, promotes aggregation of tricarboxylic acid cycle components, destabilizes iron-sulfur cluster proteins, and elicits FDX1- and protein lipoylation-dependent proteotoxic stress. This mechanism should be distinguishe

APN Inhibitor Bestatin Induces MM Cell Differentiation Through the CD79B/BTK/STAT3 Pathway.

Differentiation therapy holds significant potential for the treatment of multiple myeloma (MM). We previously identified that the aminopepti … ation of the differentiation marker CD49e, increased immunoglobulin light chain secretion, elevated cellular senescence, and a concomitant suppression of cell proliferation and APN enzymatic activity. Mechanistically, Bestatin exerts its effects by downregulating the CD79B/BTK signaling pathway, thereby activating the downstream transcription factor STAT3. Consistent …

Integrated Multi-Omics Network by Physical Exercise Across Aging: Molecular Adaptation Beyond Single Signaling Pathways.

Aging is characterized by progressive molecular dysregulation across interconnected biological systems, involving alterations in epigenetic regulation, gene expression, protein homeostasis, and metabolic function. Although physical exercise is widely recognized as one of the most effective non-pharmacological interventions to promote healthy aging, the integrative molecular mechanisms underlying its systemic effects remain incompletely understood. This review proposes a multi-omic framework in which exercise acts as a coordinated biological stimulus capable of remodeling age-associated molecul

Luteolin alleviates cyclophosphamide-induced premature ovarian failure in rats by regulating RNF8/HDAC2.

ObjectiveThe study aimed to investigate the role of luteolin in alleviating POF and its underlying molecular mechanisms.MethodsPOF model was established in rats by intraperitoneal injection of 100 mg/kg cyclophosphamide. Then, rats in the treatment group received intragastric administration of with luteolin at doses of 25 mg/kg, 50 mg/kg and 100 mg/kg, respectively. Rats in POF model group were administered the same volume of saline intragastrically. The concentrations of E2, FSH, AMH, P, LH, SOD and MDA in serum were quantified using ELISA kits. H&E and TUNEL staining were employed to assess

Ferritinophagy: multifaceted roles and potential therapeutic strategies in liver diseases.

Ferritinophagy, the selective autophagic degradation of ferritin to release iron, is emerging as a critical regulator of iron homeostasis and a key player in the pathogenesis of various liver diseases. This review comprehensively examines the mechanisms, regulation, and multifaceted roles of ferritinophagy in liver health and disease. Ferritinophagy is intricately regulated by several factors, including Nuclear Receptor Coactivator 4 (NCOA4), Iron regulatory proteins and signaling pathways such as mTOR and AMPK. These regulatory mechanisms ensure proper iron utilization and prevent iron overlo

Systematic Ocular Phenotyping of Knockout Mouse Lines Identifies Genes Associated With Age-Related Corneal Dystrophies.

PURPOSE: This study investigates genes contributing to late-adult corneal dystrophies (LACDs) in aged mice, with potential implications for … ch as pluripotency of stem cells, MAPK signaling, WNT signaling, actin cytoskeleton regulation, and cellular senescence. CONCLUSIONS: This study identified 14 genes linked to LACD in knockout mice, 12 of which are novel in corneal biology. These genes may serve as potential therapeutic targets for treating corneal diseases in aging human populations.

[Monocyte telomere length as a novel biomarker of macular atrophy and response to anti-VEGF therapy in age-related macular degeneration].

UNLABELLED: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. Monocyte telomere length is proposed as a marker of cellular senescence in this condition. PURPOSE: This study investigated the association between monocyte telomere length and retinal parameters in different forms of AMD, as well as in patients receiving antiangiogenic therapy. MATERIAL AND METHODS: Monocyte telomere length was measured in 84 patients (mean age 79±9 years) divided into four groups: non-exudative AMD with geographic atrophy (neAMD-GA), neovascular AMD (nAMD) with…

Tannic acid prevents UVB-induced skin photoaging by regulating ferroptosis through NRF2/SLC7A11/GPX4 signaling.

BACKGROUND: Photoaging is a significant contributor to accelerated skin aging, primarily driven by ultraviolet B (UVB) radiation exposure, w … skin fibroblast (HSF) cells. we measured cell viability, reactive oxygen species (ROS), markers of cellular senescence, and the activity of antioxidant enzymes. The potential mechanism of TA was explored using RNA sequencing and further verified by Western blotting and administration of ferroptosis inducers. In vivo, we employed a UVB-induced Balb/C mouse model of p …

Comparative Analysis of Aging-related Metabolic and Biological Markers between Cancer Survivors and Healthy Populations: A Systematic Review.

Cancer survivors may exhibit biological and metabolic changes linked to both cancer and its treatment. This systematic review aimed to compare metabolic and biological aging-related biomarkers between cancer survivors and healthy individuals. The primary electronic databases utilized to search papers from 2019 to 2024 were PubMed, Scopus, and Web of Science. Boolean operators were combined with specific keywords and MESH terms in searching the articles. After excluding protocol papers, studies with incorrect designs or populations, and animal studies, 27 articles were selected for data extract

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… Furthermore, hypermethylation on the P16INK4a gene, known as the tumor suppressor gene suggests an increase in the risk of cancer, which may reflect an accelerated cellular senescence [ 63 ]. … Besides that, hypermethylated miR-125b might contribute to cellular senescence, and this process is often marked by an increase in senescence-associated beta-galactosidase (SA-β-gal) activity [ 77 ]. …

Tertiary lymphoid structures: chronic inflammatory microenvironments in kidney diseases.

Chronic kidney disease is a global health problem with high morbidity and mortality rates. Acute kidney injury substantially increases the risk of chronic kidney disease progression, particularly in the elderly, partly because of prolonged inflammation that exacerbates kidney fibrosis and dysfunction. Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates that develop in non-lymphoid organs during chronic inflammation, such as autoimmune diseases, cancers, and age-related inflammation. Age-dependent TLS formation is observed in various organs, such as the kidneys, bladder, lacrima

Association Between Body Iron Status and Biological Aging.

BACKGROUND/OBJECTIVES: Iron is necessary for bodily function, but abnormal levels can increase the risk of chronic diseases. Studies of leukocyte telomere length suggest blood iron levels are positively associated with cellular senescence and accelerated aging. However, associations between blood iron and more robust metrics of biological aging, specifically those based on DNA methylation, have not been examined. METHODS: In a random sample of women from the Sister Study (n = 1260) with measured serum iron (ferritin, iron, transferrin saturation), we used linear regression models to assess cr…

Integrative Review of Molecular, Metabolic, and Environmental Factors in Spina Bifida and Congenital Diaphragmatic Hernia: Insights into Mechanisms and Emerging Therapeutics.

Spina Bifida (SB) and Congenital Diaphragmatic Hernia (CDH) are complex congenital anomalies that pose significant challenges in pediatric h … ators of these genes, influencing neural development. Additionally, telomere shortening-a marker of cellular senescence-alongside disruptions in folate metabolism and maternal nutritional deficiencies, significantly increases the risk of SB. These findings underscore the crucial role of telomere integrity in maintaining neural tissue homeostasis during embryonic deve …

Transcriptome landscape of the adrenal gland and superior cervical ganglion from hypertension-induced left ventricular hypertrophy rat model.

BACKGROUND: Hypertension-induced left ventricular hypertrophy (LVH) is a cardiac structural remodeling and dysfunction resulting from chroni … ctional analysis revealed that these DEGs were involved in pathways related to immune inflammation, cellular senescence, metabolic responses, and synaptic transmission. We also identified the top 20 hub genes specific to each of the three organs. PPI network analysis showed that these hub genes were highly interconnected and clustered into three functional modules. K …

EndoCompass project: research roadmap for calcium and bone endocrinology.

BACKGROUND: Endocrine science remains underrepresented in European Union research programmes despite the fundamental role of hormone health … ne mass acquisition, secondary osteoporosis, and skeletal dysplasias. Special emphasis is placed on cellular senescence, sex-specific differences in disease manifestation, and development of novel diagnostic tools for bone quality assessment. CONCLUSIONS: This component of the EndoCompass project provides an evidence-based roadmap for strategic research investment. …

Dolutegravir plus lamivudine downregulates cellular stress responses vs. three-drug HIV regimens.

OBJECTIVE: To compare the systemic and immune effects of two-drug regimens (2DR) and three-drug regimens (3DR) in people with HIV (PWH). DE … overlapping downregulated genes across all 3DR vs. 2DR comparisons, linked to chromatin structure, cellular senescence, stress response, and cytokine activity. Cytokine production was similar across 2DR and 3DR groups, except for enhanced interleukin (IL)-17 production in DTG + TDF + FTC users. CONCLUSIONS: Reducing NRTIs in DTG-based 2DR, particularly by omitting …

Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice.

Ovarian aging is characterized by declines in follicular reserve and the emergence of mitochondrial dysfunction, reactive oxygen species production, inflammation, and fibrosis, which eventually results in menopause. Menopause is associated with increased systemic aging and the development of numerous comorbidities; therefore, the attenuation of ovarian aging could also delay systemic aging processes in women. Recent work has established that the anti-diabetic drug Canagliflozin (Cana), a sodium-glucose transporter 2 inhibitor, elicits benefits on aging-related outcomes, likely through the modu

Bone marrow mesenchymal stem cell-derived exosomes shuttle microRNAs to endometrial stromal fibroblasts that promote tissue proliferation /regeneration/ and inhibit differentiation.

BACKGROUND: Human bone marrow-derived stem cells (hBMDSCs) are well characterized mediators of tissue repair and regeneration. An increasing … . MiR-21 is associated with several signaling pathways involved in tissue regeneration, quiescence, cellular senescence, and fibrosis. Both miR-100-5p and miR-143-3p promoted cell proliferation. MiR-100-5p specifically promoted regenerative processes by upregulating TGF-ß3, VEGFA, MMP7, and HGF. MiR-100-5p blocked differentiation or decidualization as evidenced by mo …

RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats.

INTRODUCTION: Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion … ) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats. CONCLUSION: EP can improve CIRI in vivo, the mechanism may relate to TIMP1 e …

microRNA Expression Profile in Obesity-Induced Kidney Disease Driven by High-Fat Diet in Mice.

Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney injury and dysfunction in obesity-associated nephropathy remain unclear. The present study aimed to unveil the kidney microRNA (miRNA) expression profile in a model of obesity-induced kidney disease in C57BL/6J mice using next-generation sequencing (NGS) analysis. High-fat diet (HFD)-induced obesity led to notable structural alterations in tubular and glomerular regions of the kidney, increased renal expression of proinflammatory and profibrotic genes, as well a

Exploring the therapeutic potential of puerarin on intervertebral disc degeneration by regulating apoptosis of nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) stands as a prevalent chronic orthopedic ailment, profoundly impacting patients' well-being due to i … pharmacology indicating puerarin's potential efficacy in IVDD treatment by modulating apoptosis and cellular senescence pathways. Further experiments elucidate puerarin's capacity to stimulate NP cell proliferation while inhibiting apoptosis, potentially contributing to IVDD mitigation. Western blot and PCR outcomes reveal escalated expression of apoptosis-related pr …