Details

Autor(en) / Beteiligte

• Ansari, Md. Meraj
• Ghosh, Mrinmoy
• Lee, Dong-Sun
• Son, Young-Ok

Titel

Senolytic therapeutics: An emerging treatment modality for osteoarthritis

Ist Teil von

• Ageing research reviews, 2024-04, Vol.96, p.102275-102275, Article 102275

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the elderly. It is characterized by lingering pain and increasing deterioration of articular cartilage. Aging and accumulation of senescent cells (SCs) in the joints are frequently associated with OA. Apoptosis resistance; irreversible cell cycle arrest; increased p16INK4a expression, secretion of senescence-associated secretory phenotype factors, senescence-associated β-galactosidase levels, secretion of extracellular vesicles, and levels of reactive oxygen and reactive nitrogen species; and mitochondrial dysregulation are some common changes in cellular senescence in joint tissues. Development of OA correlates with an increase in the density of SCs in joint tissues. Senescence-associated secretory phenotype has been linked to OA and cartilage breakdown. Senolytics and therapeutic pharmaceuticals are being focused upon for OA management. SCs can be selectively eliminated or killed by senolytics to halt the pathogenesis and progression of OA. Comprehensive understanding of how aging affects joint dysfunction will benefit OA patients. Here, we discuss age-related mechanisms associated with OA pathogenesis and senolytics as an emerging modality in the management of age-related SCs and pathogenesis of OA in preclinical and clinical studies. [Display omitted] •Senescence in joint tissue accelerates osteoarthritis.•Senescent cells (SCs) exhibit increased SA-β-gal activity and p16 upregulation.•Increase in SCs and SASP factors can promote osteoarthritis development.•Senolytics can eliminate SCs by targeting signaling pathways active in these cells.•Targeted removal of SCs offers a promising avenue for osteoarthritis treatment.