Clock gene Bmal1 influences the cell cycle of chondrocytes in osteoarthritis DOI
Chunsheng Yang, Mi Chen,

Zulifeiya Aletengbieke

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Abstract Osteoarthritis (OA) is a degenerative disease caused by multiple factors. This study used in vitro and animal models to investigate the connection between biological clock cell cycle osteoarthritic cartilage. The results indicate that transcription levels of circadian gene Bmal1 exhibit negative correlation with Mmp13 positive Wee1. Thus, increased expression Wee1 may be potential protective factor osteoarthritis, while high Per1, Cdk1, Ccnb1, risk factor. By controlling contributing pathophysiology OA, impact apoptosis chondrocytes.

Language: Английский

Cellular senescence in the tumor with a bone niche microenvironment: friend or foe? DOI Creative Commons

Sajad Alavimanesh,

Negar Nayerain Jazi,

Maedeh Choubani

et al.

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 23, 2025

Cellular senescence is understood to be a biological process that defined as irreversible growth arrest and was originally recognized tumor-suppressive mechanism prevents further propagation of damaged cells. More recently, cellular has been shown have dual role in prevention tumor promotion. Senescent cells carry senescence-associated secretory phenotype (SASP), which altered by factors including pro-inflammatory cytokines, chemokines, other proteases, leading the alteration tissue microenvironment. Though would eventually halt cancerous potential cells, SASP contributes environment promoting inflammation, matrix remodeling, cell invasion. The paradox prevention/promotion particularly relevant bone niche microenvironment, where longer-lasting, chronic inflammation promotes formation. Insights into mechanistic understanding provide basis for targeted therapies, such senolytics, aim eliminate senescent or inhibitors, tumor-promoting effects senescence. These therapeutic interventions offer significant clinical implications treating cancer healthy aging.

Language: Английский

Citations

2
Epigenetic regulations of cellular senescence in osteoporosis DOI
Shaochuan Huo,

Xinzheng Tang,

Weijian Chen

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102235 - 102235

Published: Feb. 16, 2024

Language: Английский

Citations

17
Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence DOI Creative Commons
Jing Hou, Kaixuan Chen,

Chen He

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(11), P. 1562 - 1581

Published: Sept. 12, 2024

The accumulation and systemic propagation of senescent cells contributes to physiological aging age-related pathology. However, which cell types are most susceptible the aged milieu could be responsible for senescence has remained unclear. Here we found that physiologically bone marrow monocytes/macrophages (BMMs) propagate multiple tissues, through extracellular vesicles (EVs), drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target microRNAs within BMM-EVs regulates downstream effects on dysfunction. Demonstrating therapeutic potential, report treatment with PPARα agonist fenofibrate effectively restores tissue homeostasis Suggesting conservation humans, cohort study 7,986 participants, use is associated reduced risk chronic disease higher life expectancy. Together, our findings establish BMMs can distant tissues cause dysfunction, they provide supportive evidence extend healthy lifespan.

Language: Английский

Citations

17
Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing DOI Creative Commons

Nan-Yu Zou,

Ran Liu, Mei Huang

et al.

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 25, 2024

Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes SSPC remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during which triggers and impairs fracture healing. Local injection human rGCA young mice induced delayed repair. Genetic deletion Gca monocytes/macrophages was sufficient to rejuvenate repair aged alleviate senescence. Mechanistically, GCA binds plexin-B2 receptor activates Arg2-mediated mitochondrial dysfunction, resulting cellular Depletion Plxnb2 SSPCs impaired Administration GCA-neutralizing antibody enhanced healing mice. Thus, our study senescent within trigger secondary senescence, neutralization represents promising therapy for nonunion or union elderly individuals.

Language: Английский

Citations

11
Proteostasis disruption and senescence in Alzheimer’s disease pathways to neurodegeneration DOI
Riya Thapa, Asif Ahmad Bhat, Moyad Shahwan

et al.

Brain Research, Journal Year: 2024, Volume and Issue: 1845, P. 149202 - 149202

Published: Aug. 30, 2024

Language: Английский

Citations

9
Unveiling the ageing-related genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning DOI Creative Commons
Jian Huang, Lu Wang,

Jiangfei Zhou

et al.

Artificial Cells Nanomedicine and Biotechnology, Journal Year: 2025, Volume and Issue: 53(1), P. 57 - 68

Published: March 1, 2025

Ageing significantly contributes to osteoarthritis (OA) and metabolic syndrome (MetS) pathogenesis, yet the underlying mechanisms remain unknown. This study aimed identify ageing-related biomarkers in OA patients with MetS. MetS datasets genes (ARGs) were retrieved from public databases. The limma package was used differentially expressed (DEGs), weighted gene coexpression network analysis (WGCNA) screened modules, machine learning algorithms, such as random forest (RF), support vector (SVM), generalised linear model (GLM), extreme gradient boosting (XGB), employed. nomogram receiver operating characteristic (ROC) curve assess diagnostic value, CIBERSORT analysed immune cell infiltration. We identified 20 intersecting among DEGs of OA, key module MetS, ARGs. By comparing accuracy four models for disease prediction, SVM model, which includes CEBPB, PTEN, ARPC1B, PIK3R1, CDC42, selected. These hub ARGs not only demonstrated strong values based on data but also exhibited a significant correlation Building these findings, we have five that are associated infiltration constructed at early diagnosing

Language: Английский

Citations

1
Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions DOI Open Access
Merin Lawrence, Abhishek Goyal, Shelly Pathak

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7411 - 7411

Published: July 5, 2024

Advancing age is associated with several age-related diseases (ARDs), musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic contributing towards considerable number patients, a deeper understanding bone aging the need hour. One underlying factors cellular senescence and its secretory phenotype (SASP). SASP comprises pro-inflammatory markers, cytokines chemokines that arrest cell growth development. The accumulation over years leads to chronic low-grade inflammation advancing age, also known as inflammaging. pathways molecular mechanisms focused on inflammaging are currently limited but increasingly being explored. Most genes, involved in coincide those cancer other ARDs like osteoarthritis (OA). Thus, exploring these using techniques sequencing, identifying combatting them most suitable approach crucial for healthy early detection ARDs. Several approaches can be used aid regeneration reduce bone. These may pharmacological, non-pharmacological lifestyle interventions. increasing evidence intricate relationship between aging, senescence, ARDs, anti-aging strategies marrow (BM).

Language: Английский

Citations

6
Targeting miR-29 mitigates skeletal senescence and bolsters therapeutic potential of mesenchymal stromal cells DOI
Zhen Ding, Guixing Ma, Bo Zhou

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(8), P. 101665 - 101665

Published: Aug. 1, 2024

Language: Английский

Citations

5
10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically DOI Creative Commons

Nana Geng,

Mengtian Fan,

Biao Kuang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 4, 2024

Language: Английский

Citations

4
Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study DOI Creative Commons

Xiuli Yang,

Jiekang Wang, Yuguo Li

et al.

Published: Feb. 11, 2025

Article Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study Xiuli Yang 1,†, Jiekang Wang 2,3,†, Yuguo Li 1,4, Mei Wan 2,3,*, Zhiliang Wei 1,4,* 1 Russell H. Morgan Department of Radiology Radiological Science, Johns Hopkins University School Medicine, Baltimore, MD 21205, USA 2 Orthopaedic Surgery, 3 Biomedical Engineering, 4 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, * Correspondence: [email protected] (M.W.); [email protected] (Z.W.) † These authors contributed equally this work. Received: 20 November 2024; Revised: December Accepted: 22 January 2025; Published: 11 February 2025 Abstract: circulating platelet-derived growth factor-BB (PDGF-BB) has been implicated the development various aged-related pathologies is recognized as a potential pro-aging factor. Although numerous studies have explored pathological roles PDGF-BB/PDGFRβ signaling pathway, few investigations dissected its function neurofunctional responses elevated PDGF-BB, primarily because in-vivo measurements are generally required assess neurofunction. To address knowledge gap, we characterized vascular metabolic vivo using multiparametric non-invasive non-contrast techniques conditional Pdgfb transgenic mouse model (PdgfbcTG) at 6 months age. Results indicated that PdgfbcTG mice exhibited decreased cerebral blood flow (p = 0.025), oxygen extraction 0.002), increased rate 0.035), mirroring changes observed human aging. The change was significantly higher (≥200.3%) compared naturally aged mice. This study provides evidence accelerates neurovascular

Language: Английский

Citations

0