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Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
Authors:Yueying Zhou,Iman M. A. Al‐  Naggar,Po‐  Jung Chen,Nathan S. Gasek,Ke Wang,Shivam Mehta,George A. Kuchel,Sumit Yadav,Ming Xu
Affiliation:1. Xiangya Stomatological Hospital and School of Stomatology, Central South University, Changsha Hunan, China ; 2. UConn Center on Aging, UConn Health, Farmington CT, USA ; 3. Center for Regenerative Medicine and Skeletal Development, UConn Health, Farmington CT, USA ; 4. Division of Orthodontics, UConn Health, Farmington CT, USA ; 5. Department of Genetics and Genome Sciences, UConn Health, Farmington CT, USA
Abstract:Aging is one of the major risk factors for degenerative joint disorders, including those involving the temporomandibular joint (TMJ). TMJ degeneration occurs primarily in the population over 65, significantly increasing the risk of joint discomfort, restricted joint mobility, and reduced quality of life. Unfortunately, there is currently no effective mechanism‐based treatment available in the clinic to alleviate TMJ degeneration with aging. We now demonstrate that intermittent administration of senolytics, drugs which can selectively clear senescent cells, preserved mandibular condylar cartilage thickness, improved subchondral bone volume and turnover, and reduced Osteoarthritis Research Society International (OARSI) histopathological score in both 23‐ to 24‐month‐old male and female mice. Senolytics had little effect on 4 months old young mice, indicating age‐specific benefits. Our study provides proof‐of‐concept evidence that age‐related TMJ degeneration can be alleviated by pharmaceutical intervention targeting cellular senescence. Since the senolytics used in this study have been proven relatively safe in recent human studies, our findings may help justify future clinical trials addressing TMJ degeneration in old age.
Keywords:aging   cellular senescence   dasatinib   quercetin   TMJ
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