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Targeting aging for disease modification in osteoarthritis

Collins, John, A.a,b,*; Diekman, Brian, O.b,c,d,*; Loeser, Richard, F.a,b

Current Opinion in Rheumatology: January 2018 - Volume 30 - Issue 1 - p 101–107
doi: 10.1097/BOR.0000000000000456
OSTEOARTHRITIS: Edited by Mukundan Attur

Purpose of review Age is a key risk factor for the development of osteoarthritis and age-related changes within the joint might represent targets for therapy. The recent literature was reviewed to find studies that provide new insight into the role of aging in osteoarthritis, with a focus on the potential for disease modification.

Recent findings Preclinical studies using isolated cells and animal models provide evidence that two hallmarks of aging (cellular senescence and mitochondrial dysfunction) contribute to the development of osteoarthritis. Senescent cells secrete pro-inflammatory mediators and matrix degrading enzymes, and killing these cells with ‘senolytic’ compounds has emerged as a potential disease-modifying therapy. Mitochondrial dysfunction is associated with increased levels of reactive oxygen species (ROS) that can promote osteoarthritis by disrupting homeostatic intracellular signaling. Reducing ROS production in the mitochondria, stimulating antioxidant gene expression through Nrf2 activation, or inhibiting specific redox-sensitive signaling proteins represent additional approaches to disease modification in osteoarthritis that require further investigation.

Summary Although no human clinical trials for osteoarthritis have specifically targeted aging, preclinical studies suggest that targeting cellular senescence and/or mitochondrial dysfunction and the effects of excessive ROS may lead to novel interventions that could slow the progression of osteoarthritis.

aDivision of Rheumatology, Allergy, and Immunology

bThurston Arthritis Research Center

cDepartment of Biomedical Engineering, University of North Carolina, Chapel Hill

dNorth Carolina State University, Raleigh, North Carolina, USA

Correspondence to Richard F. Loeser, Thurston Arthritis Research Center, Campus Box 7280, Chapel Hill, NC 27599-7280, USA. Tel: +1 919 966 7042; fax: +1 919-966-1739; e-mail:

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