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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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Autores principales: Zhou, Yueying, Al‐Naggar, Iman M. A., Chen, Po‐Jung, Gasek, Nathan S., Wang, Ke, Mehta, Shivam, Kuchel, George A., Yadav, Sumit, Xu, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282237/
https://www.ncbi.nlm.nih.gov/pubmed/34101970
http://dx.doi.org/10.1111/acel.13394
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author Zhou, Yueying
Al‐Naggar, Iman M. A.
Chen, Po‐Jung
Gasek, Nathan S.
Wang, Ke
Mehta, Shivam
Kuchel, George A.
Yadav, Sumit
Xu, Ming
author_facet Zhou, Yueying
Al‐Naggar, Iman M. A.
Chen, Po‐Jung
Gasek, Nathan S.
Wang, Ke
Mehta, Shivam
Kuchel, George A.
Yadav, Sumit
Xu, Ming
author_sort Zhou, Yueying
collection PubMed
description 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.
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spelling pubmed-82822372021-07-16 Senolytics alleviate the degenerative disorders of temporomandibular joint in old age Zhou, Yueying Al‐Naggar, Iman M. A. Chen, Po‐Jung Gasek, Nathan S. Wang, Ke Mehta, Shivam Kuchel, George A. Yadav, Sumit Xu, Ming Aging Cell Short Takes 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. John Wiley and Sons Inc. 2021-06-08 2021-07 /pmc/articles/PMC8282237/ /pubmed/34101970 http://dx.doi.org/10.1111/acel.13394 Text en © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Takes
Zhou, Yueying
Al‐Naggar, Iman M. A.
Chen, Po‐Jung
Gasek, Nathan S.
Wang, Ke
Mehta, Shivam
Kuchel, George A.
Yadav, Sumit
Xu, Ming
Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
title Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
title_full Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
title_fullStr Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
title_full_unstemmed Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
title_short Senolytics alleviate the degenerative disorders of temporomandibular joint in old age
title_sort senolytics alleviate the degenerative disorders of temporomandibular joint in old age
topic Short Takes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282237/
https://www.ncbi.nlm.nih.gov/pubmed/34101970
http://dx.doi.org/10.1111/acel.13394
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