Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Сен. 26, 2024
Язык: Английский
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Сен. 26, 2024
Язык: Английский
Nature Aging, Год журнала: 2024, Номер 4(11), С. 1562 - 1581
Опубликована: Сен. 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.
Язык: Английский
Процитировано
22Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102235 - 102235
Опубликована: Фев. 16, 2024
Язык: Английский
Процитировано
19Clinical and Experimental Medicine, Год журнала: 2025, Номер 25(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
3Bone Research, Год журнала: 2024, Номер 12(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
14Brain Research, Год журнала: 2024, Номер 1845, С. 149202 - 149202
Опубликована: Авг. 30, 2024
Язык: Английский
Процитировано
10International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7411 - 7411
Опубликована: Июль 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).
Язык: Английский
Процитировано
7Artificial Cells Nanomedicine and Biotechnology, Год журнала: 2025, Номер 53(1), С. 57 - 68
Опубликована: Март 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
Язык: Английский
Процитировано
1Cell Reports Medicine, Год журнала: 2024, Номер 5(8), С. 101665 - 101665
Опубликована: Авг. 1, 2024
Язык: Английский
Процитировано
5Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Сен. 4, 2024
Язык: Английский
Процитировано
5Biomedicines, Год журнала: 2024, Номер 12(9), С. 1948 - 1948
Опубликована: Авг. 26, 2024
The aging of the world population is closely associated with an increased prevalence musculoskeletal disorders, such as osteoporosis, sarcopenia, and osteoarthritis, due to common genetic, endocrine, mechanical risk factors. These conditions are characterized by degeneration bone, muscle, cartilage tissue, resulting in fractures reduced mobility. Importantly, a crucial role pathophysiology these diseases has been proposed for cellular senescence, state irreversible cell cycle arrest induced factors DNA damage, telomere shortening, mitochondrial dysfunction. In addition, senescent cells secrete pro-inflammatory molecules, called senescence-associated secretory phenotype (SASP), which can alter tissue homeostasis promote disease progression. Undoubtedly, targeting their profiles could development integrated strategies, including regular exercise balanced diet or use senolytics senomorphs, improve quality life population. Therefore, our review aimed highlight senescence age-related diseases, summarizing main underlying mechanisms potential anti-senescence strategies treatment osteoarthritis.
Язык: Английский
Процитировано
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