Format

Send to

Choose Destination
Nat Rev Rheumatol. 2016 Jul;12(7):412-20. doi: 10.1038/nrrheum.2016.65. Epub 2016 May 19.

Ageing and the pathogenesis of osteoarthritis.

Author information

1
Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, 3300 Thurston Building, Campus Box 7280, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7280, USA.
2
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, 450 West Drive, Campus Box 7295, Chapel Hill, North Carolina 27599-7295, USA.

Abstract

Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as 'inflammaging'); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5'-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition.

PMID:
27192932
PMCID:
PMC4938009
DOI:
10.1038/nrrheum.2016.65
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center