Author: Brian O Diekman1, Richard F Loeser2
Affiliation: <sup>1</sup> Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, 27599, USA. Electronic address: bdiekman@email.unc.edu.
<sup>2</sup> Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA; Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address: richard_loeser@med.unc.edu.
Conference/Journal: Osteoarthritis Cartilage
Date published: 2023 Dec 2
Other:
Pages: S1063-4584(23)00997-4 , Special Notes: doi: 10.1016/j.joca.2023.11.018. , Word Count: 257
Objective:
The correlation between age and incidence of osteoarthritis (OA) is well known but the causal mechanisms involved are not completely understood. This narrative review summarizes selected key findings from the past 30 years that have elucidated key aspects of the relationship between aging and OA.
Methods:
The peer-reviewed English language literature was searched on PubMed using key words including senescence, aging, cartilage, and osteoarthritis, for original studies and reviews published from 1993-2023 with a major focus on more recent studies. Manuscripts most relevant to aging and OA that examined one or more of the hallmarks of aging were selected for further review.
Results:
All proposed hallmarks of aging have been observed in articular cartilage and some have also been described in other joint tissues. Hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled macroautophagy, chronic inflammation, and dysbiosis. There is evidence that these age-related changes contribute to the development of OA in part by promoting cellular senescence. Senescence may therefore serve as a downstream mediator that connects numerous aging hallmarks to OA, likely through the senescence-associated secretory phenotype (SASP) that is characterized by increased production of proinflammatory cytokines and matrix metalloproteinases.
Conclusions:
Progress over the past 30 years has provided the foundation for emerging therapies, such as senolytics and senomorphics, that hold promise for OA disease modification. Mechanistic studies utilizing physiologically-aged animals and cadaveric human joint tissues will be important for continued progress.
Keywords: Aging; Chondrocyte; cartilage; senescence.
PMID: 38049031 DOI: 10.1016/j.joca.2023.11.018