Senolytics alleviate the degenerative disorders of temporomandibular joint in old age

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...

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Bibliographic Details
Published in:Aging cell 2021-07, Vol.20 (7), p.e13394-n/a
Main Authors: Zhou, Yueying, Al‐Naggar, Iman M. A., Chen, Po‐Jung, Gasek, Nathan S., Wang, Ke, Mehta, Shivam, Kuchel, George A., Yadav, Sumit, Xu, Ming
Format: Article
Language:English
Subjects:
Age
Aging
Alzheimer's disease
Animals
Bone density
Bone turnover
Bones
Cartilage
Cartilage diseases
cellular senescence
Clinical trials
dasatinib
Degeneration
Gender differences
Human subjects
Humans
Male
Mice
Osteoarthritis
Phosphatase
Quality of life
quercetin
Risk factors
Senescence
Senotherapeutics - pharmacology
Senotherapeutics - therapeutic use
Short Take
Short Takes
Stains & staining
Subchondral bone
Temporomandibular joint
Temporomandibular Joint - pathology
Temporomandibular Joint Disorders - drug therapy
TMJ
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Summary: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. Senolytic drugs preserved mandibular condylar cartilage thickness, improved subchondral bone volume and turnover, and reduced pathologies in old mouse TMJs.
ISSN:1474-9718
1474-9726
DOI:10.1111/acel.13394