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Photobiomodulation therapy reduces diabetic periodontal damage through modulation of macrophage metabolism and functions.

Diabetes mellitus disrupts macrophage function and immune homoeostasis, thereby increasing susceptibility toward periodontitis. PBMT shows emerging potential in oral rehabilitation. However, it remains underexplored for targeting diabetes-associated periodontal complications. This study aimed to investigate the biomodulatory effects of PBMT on hyperglycaemia-associated macrophage dysfunction, metabolic disorders, and periodontal tissue impairment. Immortalized bone marrow-derived macrophages undergoing glucose transition and streptozotocin-induced diabetic mice received PBMT (980 nm, 3 J/cm²),

A partial differential equation model of a novel treatment for chronic wound biofilm infections.

BACKGROUND: Chronic wounds, such as pressure ulcers, venous leg ulcers, and diabetic foot ulcers, present a significant healthcare challenge due to their prolonged healing times and association with biofilm infections. This study introduces a mathematical model to investigate wound healing dynamics during the proliferative stage, focusing on chronic wound conditions characterised by poor vascularisation, clotting deficiencies, cellular senescence, and bacterial biofilms. METHODS: The model examines the interactions between fibroblasts, keratinocytes, granulation tissue, nutrients, and signall…

Age-related GSS promoter methylation in BMSCs drives osteoporosis and the reversal by targeted GSH delivery.

Age-related osteoporosis arises from bone tissue with inadequate metabolic support for osteogenesis. We identified that DNA methylation-medi … stem sustainably delivers GSH, alleviates oxidative stress, improves mitochondrial function, delays cellular senescence, and promotes osteogenesis. In summary, while DNA methylation acts upstream to constrain GSH synthesis in aging bone, therapeutically correcting the resultant metabolic deficit via bone-homing exosome-mediated GSH delivery restores osteogenic functi …

GenX-associated molecular signatures overlap with testicular aging and male infertility: a multi-omics integration analysis.

GenX (HFPO-DA), a short-chain per- and polyfluoroalkyl substance (PFAS) substitute, is implicated in testicular toxicity. GenX-related genes … O3 were upregulated, while POLB was downregulated. Functional enrichment implicated FoxO signaling, cellular senescence, and DNA repair pathways. Molecular docking confirmed favorable GenX-protein binding interactions. SOD1, XRCC5, FOXO3, and POLB are candidate biomarkers for GenX-induced reproductive toxicity, with oxidative stress and genome maintenance as key path …

Different ages of gut microbiota diversity and metabolic pattern in rhesus macaques.

INTRODUCTION: The gut microbiota and its metabolites change dynamically with age, but their trajectories and links to healthy aging are uncl … ing hepatic ammonia metabolism. DISCUSSION: Ornithine or a-ketoglutarate supplementation mitigates cellular senescence in liver cells and bone marrow mesenchymal stem cells. Our findings elucidate the dynamic changes of gut microbiota and metabolites with age, providing critical support for the use of rhesus monkeys as an animal model to study the role of gut microb …

NNMT as a therapeutic target in fibrosis: Insights from the heart, liver, kidneys, and lungs.

Fibrosis, a key pathological process in chronic diseases, involves excessive extracellular matrix deposition that causes organ dysfunction. … also exhibits organ-specific mechanisms such as influencing hepatic stellate cells in the liver and cellular senescence in the kidneys. Given its central role in driving fibrogenesis, developing potent and selective NNMT inhibitors has emerged as an urgent therapeutic priority. Current therapeutic strategies targeting NNMT include small-molecule inhibitors, gene-base …

Microglial immunometabolism in Alzheimer's disease: A stage-resolved trajectory from adaptive remodeling to the metabolic paradox.

Microglia are central regulators of the cellular phase of Alzheimer's disease (AD). Under chronic exposure to amyloid-β, pathological tau, and aging-associated bioenergetic decline, these cells undergo immunometabolic remodeling that may initially be adaptive. As stress persists, this remodeling can become maladaptive, marked by disordered glycolysis, disturbed lipid handling, mitochondrial dysfunction, and compensatory failure. In this review, we organize these changes as a stage-dependent trajectory from adaptive remodeling to functional decompensation. We introduce the "metabolic paradox" a

A matter of balance: Heme oxygenase-1 at the crossroads of healthy and pathological aging.

Increasing life expectancy has led to a growing prevalence of age-related disorders, including dementia, cardiovascular disease, frailty, osteoporosis, sarcopenia, and cancer. Heme oxygenase-1 (HO-1), a stress-inducible enzyme that degrades heme into carbon monoxide (CO), biliverdin which is then reduced to bilirubin by the biliverdin reductase enzyme, and iron, has emerged as a key regulator of several hallmarks of aging, including oxidative stress, inflammation, autophagy, mitochondrial dysfunction, and cellular senescence. This review evaluates age-associated changes in HO-1 expression acro…

Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation.

NeuroHIV has emerged as a significant unmet challenge, manifesting as impairments in learning, memory, sensorimotor, and language in people … ng non-coding RNAs and extracellular vesicles-in microglial activation through mechanisms including cellular senescence, ferroptosis, defective mitophagy, NLR family pyrin domain containing 3 activation, and NF-κB pathway modulation. These processes collectively lead to neuroinflammation and the development of NeuroHIV. This review presents the current understanding …

A new approach to an old disease: Ageing, arrhythmogenic substrate and the role of risk-factor modification in atrial fibrillation.

Atrial fibrillation (AF) prevalence rises sharply with age due to two independent mechanisms. Ageing produces irreversible arrhythmogenic substrate changes through progressive fibrosis, cellular senescence and mitochondrial dysfunction, while modifiable risk factors such as obesity, hypertension, sleep apnoea, diabetes and alcohol use promote atrial remodelling through inflammatory, haemodynamic and metabolic pathways. These comorbidities accumulate with age but operate through distinct mechanisms. Late gadolinium enhancement magnetic resonance imaging now quantifies fibrosis burden, while cir…

Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention.

This study utilizes single-cell RNA sequencing data to reveal the transcriptomic characteristics of breast cancer and normal epithelial cells. Nine significant cell populations were identified through stringent quality control and batch effect correction. Further classification of breast cancer epithelial cells based on the PAM50 method and clinical subtypes highlighted significant heterogeneity between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC). The study also analyzed myeloid cells and tumor-infiltrating lymphocytes (TILs) within the breast cancer immu

Translated retained intron 11 sequence confers pathological properties to Tau in Alzheimer's disease.

A novel Tau11i isoform was previously found to be enriched in Alzheimer's disease (AD) brains. Further characterization showed that the 19-amino acid peptide encoded by retained intron 11 facilitates the formation of high-molecular-weight heterodimers and phase-separated liquid droplets, as well as enhances heparin-induced β-sheet aggregation and cellular seeding of Tau11i. Compared to full-length Tau441 isoform, expression of Tau11i in human neurons caused significant transcriptional changes that recapitulated single-cell molecular signatures of neurofibrillary tangle (NFT)-free excitatory AD

Alu RNA-transfected Primary Mouse Retinal Pigment Epithelium: A Pathologically Relevant In Vitro Model for Age-related Macular Degeneration.

Age-related macular degeneration (AMD), particularly non-exudative AMD, requires experimental models that better replicate human pathology. … lu RNA transfection: inflammatory cytokine secretion (mouse genes Ifn-β, Il-6, Tnf-α; p < 0.05) and cellular senescence (mouse genes p21 and p53 upregulation; p < 0.05). Compared to traditional acute stress models, this system recapitulates chronic inflammatory-degenerative cascades of AMD through standardized techniques, ensuring reproducibility. By combining aspect …

Chemerin's Role in Endometrial Dysfunction: Insights From Transcriptomic Analysis.

Endometrium, the lining of the uterus, changes dynamically in response to fluctuations in ovarian hormones. The proper endocrine environment … inhibited lipid metabolism and induced the epithelial-mesenchymal transition (EMT)-like process and cellular senescence. More importantly, GSEA and immunoblots showed that chemerin restrained the STAT3 signalling pathway, which is required for endometrial receptivity establishment. Collectively, these findings provide new evidence that over-produced chemerin underlyi …

Disease pathogenicity in Hutchinson-Gilford progeria syndrome mice: insights from lung-associated alterations.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by accelerated aging, impaired growth, disr … ng tissue from the HGPS mouse model revealed elevated Progerin expression, abnormal NAD metabolism, cellular senescence markers (higher level of p16 and p27, lower level of ki67), and various age-related morphology changes, including fibrosis, inflammation, and thickening of alveolar walls. Transcriptomic analyses of lung tissue indicated that down-regulated genes (T …

Frailty in Pulmonary Hypertension: A Multidimensional Comorbidity.

Pulmonary hypertension is a complex and irreversible pulmonary vascular disease with a significant impact on patients' lives. Pulmonary hypertension is categorized into five groups according to its etiology. Frailty is a multifaceted disorder that leads to physical, social, cognitive, and psychological decline. Several studies have linked a high occurrence of frailty to heart failure and chronic lung diseases, but the prevalence and impact of frailty in pulmonary arterial hypertension (PAH) remain largely unexplored. At the molecular level, inflammation, oxidative stress, cellular senescence, …

Targeting the Electron Transport System for Enhanced Longevity.

Damage to mitochondrial DNA (mtDNA) results in defective electron transport system (ETS) complexes, initiating a cycle of impaired oxidative phosphorylation (OXPHOS), increased reactive oxygen species (ROS) production, and chronic low-grade inflammation (inflammaging). This culminates in energy failure, cellular senescence, and progressive tissue degeneration. Rapamycin and metformin are the most extensively studied longevity drugs. Rapamycin inhibits mTORC1, promoting mitophagy, enhancing mitochondrial biogenesis, and reducing inflammation. Metformin partially inhibits Complex I, lowering rev…

Network Pharmacology Combined with Experimental Validation to Investigate the Effects and Mechanisms of Aucubin on Aging-Related Muscle Atrophy.

Aucubin (AU) is one of the main components of the traditional Chinese medicine Eucommia ulmoides Oliv (EU). This study investigated the effects of AU on aging-related skeletal muscle atrophy in vitro and in vivo. The results of network pharmacology revealed the potential therapeutic effects of AU on muscle atrophy. In vitro, AU effectively attenuated D-gal-induced cellular damage, reduced the number of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, down-regulated the expression levels of muscle atrophy-related proteins Atrogin-1 and MuRF1, and improved myotube differentiation

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

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… Recent studies have revealed that a genetic reduction in activity of nutrient‐sensing network components could potentially prolong a healthy lifespan in a spectrum of animal models. 29 Cellular senescence : Cellular senescence is a response elicited from stress and injury such as DNA damage, replicative … Inactivating KAT7 in human stem cells reduced histone H3 lysine 14 acetylation, suppressed p15 INK4b transcription, and mitigated cellular senescence. …

Specific inhibition of fibroblast growth factor receptor 1 signaling by a DNA aptamer.

Impaired fibroblast growth factor receptor (FGFR) signaling is associated with many human conditions, including growth disorders, degenerati … cells, VZ23 inhibited the activation of downstream FGFR1 signaling and FGFR1-mediated regulation of cellular senescence, proliferation, and extracellular matrix homeostasis. Consistent with the specificity toward FGFR1 observed in vitro, VZ23 did not inhibit FGFR2-4 signaling in cells. We show that the VZ23 inhibits FGFR1 signaling in the presence of cognate fibrobla …