Hindawi Publishing Corporation Journal of Aging Research Volume 2012, Article ID 950192, 7 pages doi:10.1155/2012/950192 Review Article Aging and Osteoarthritis: An Inevitable Encounter? Thomas H u¨gle,1, 2 Jeroen Geurts,1 Corina N u¨esch,1 Magdalena M u¨ller-Gerbl,3 and Victor Valderrabano1 1 Osteoarthritis Research Center, Department of Orthopaedic Surgery, University Hospital Basel, Basel University, Spitalstrasse 21, 4031 Basel, Switzerland 2 Department of Rheumatology, University Hospital Basel, Felix-Platter-Spital, 4012 Basel, Switzerland 3 Institute of Anatomy, University of Basel, 4056 Basel, Switzerland Correspondence should be addressed to Thomas Hu¨gle, thomas.huegle@unibas.ch Received 24 February 2012; Accepted 28 March 2012 Academic Editor: Iris Reuter Copyright © 2012 Thomas H u¨gle et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Osteoarthritis (OA) is a major health burden of our time. Age is the most prominent risk factor for the development and progression of OA. The mechanistic inﬂuence of aging on OA has diﬀerent facets. On a molecular level, matrix proteins such as collagen or proteoglycans are modiﬁed, which alters cartilage function. Collagen cross-linking within the bone results in impaired plasticity and increased stiﬀness. Synovial or fat tissue, menisci but also ligaments and muscles play an important role in the pathogenesis of OA. In the elderly, sarcopenia or other causes of muscle atrophy are frequently encountered, leading to a decreased stability of the joint. Inﬂammation in form of cellular inﬁltration of synovial tissue or subchondral bone and expression of inﬂammatory cytokines is more and more recognized as trigger of OA. It has been demonstrated that joint movement can exhibit anti-inﬂammatory mechanisms. Therefore physical activity or physiotherapy in the elderly should be encouraged, also in order to increase the muscle mass. A reduced stem cell capacity in the elderly is likely associated with a decrease of repair mechanisms of the musculoskeletal system. New treatment strategies, for example with mesenchymal stem cells (MSC) are investigated, despite clear evidence for their eﬃcacy is lacking. 1. Introduction Half of all persons aged over 65 suﬀer from osteoarthritis (OA) [1]. As a matter of fact, age is the most prominent risk factor for the initiation and progression of OA. The common explanation for this is the cumulative eﬀect of mechanical load over the years, resulting clinically in “wear and tear” and pathologically in cartilage breakdown [2]. Therefore, OA has been regarded as a naturally occurring, irreversible disorder, rather than a speciﬁc, potentially treatable disease. During the last decade, however, it became clearer that OA is not a purely mechanical problem. Inﬂammatory and metabolic processes are substantially involved in the pathogenesis and progression of OA. Not only cartilage, but also subchondral bone, menisci, muscles as well as fat, and synovial tissues play an important role, notably in the early phase of OA (Figure 1). Therefore, OA has been referred to as a “whole joint disease.” Despite a higher complexity, this concept has not only improved our understanding of the disease but also indicates potentially new treatment strategies. To understand why aging predisposes to the development of OA, a link between aging processes and the pathological changes in the OA joint needs to be established. On a mole- cular level, aging research has revealed intrinsic changes in the structure of extracellular matrix proteins such as col- lagen or proteoglycans. Stiﬀening of the collagen network or increased glycation provoke a functional impairment of car- tilage and joint function [3]. Aging also has profound eﬀects on cellular processes notably leading to enhanced apopto- sis and reduced cellular regeneration [4]. Nonenzymatic collagen cross-linking leads abnormalities in bone toughness and stiﬀness. Bone plasticity is further suppressed by an increase of osteon density, which leads to a lower potency of crack-bridging mechanisms [5]. Synovitis is frequently involved in OA, notably in the early phase of the disease [6]. This has been demonstrat- ed both by histological studies and magnetic resonance imaging (MRI) analyses [7]. OA synovial ﬂuid contains proinﬂammatory cytokines. This is demonstrated clinically when a ruptured baker cyst leads to painful swelling of