Aging and osteoarthritis

Abstract

Purpose of review: Osteoarthritis is strongly linked to aging but the mechanisms for this link are incompletely understood. The recent literature was reviewed to find studies providing new insights into the connection between aging and osteoarthritis.

Recent findings: Basic aging studies in nonarticular cells suggest that a cell stress or cell damage response contributes to chronic inflammation that promotes age-related diseases. This cellular response results in the senescence-associated secretory phenotype which has many of the characteristics of an osteoarthritic chondrocyte in terms of the cytokines, chemokines, and proteases produced. Oxidative stress can promote cell senescence and studies have shown a role for oxidative stress in altering cell signaling pathways in chondrocytes that can disrupt the response to growth factors. Mitochondria are an important source of reactive oxygen species and studies continue to support a role for the mitochondria in osteoarthritis, including work suggesting changes in energy production. Cell death occurs in osteoarthritic cartilage and recent studies suggest autophagy may play a role in determining if a cell lives or dies when stressed.

Summary: Continued progress is being made on characterizing aging-related changes in cartilage. Additional studies are needed that focus on the tissues outside of the articular cartilage that play a role in osteoarthritis. Because osteoarthritis occurs in older adults who also have age-related changes in muscle, bone, fat, and the nervous system, it is likely that a more general and systemic approach will be needed to better understand the link between aging and osteoarthritis.

Figure 1

The role of chondrocyte senescence in OA. Recent studies have demonstrated several age-related changes in chondrocytes that may contribute to the development of a senescence-associated secretory phenotype (SASP) characterized by increased production of inflammatory mediators and matrix degrading enzymes. These changes include an altered response to TGFβ due to an increase in the ratio of the ALK1 to ALK5 ratio and a reduced response to IGF-1 due to increased levels of reactive oxygen species (ROS) and a reduction in Sirt1. Decreased Sirt1 and AMPK may promote the catabolic pathways associated with the SASP. The mitochondria may serve as a source of increased ROS which can cause mitochondrial and nuclear DNA damage including telomere shortening. An increase in ROS as well as a reduction in the transcriptional regulator high-mobility group box protein 2 (HMGB2) may contribute to cell death.