Ageing and the pathogenesis of osteoarthritis
By Richard F. Loeser, J. Collins, B. Diekman. Nature Reviews Rheumatology, 2016
1,139 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Pharmacology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/8e6af4ef8e952eeffed6ba357585e59aca7fe90e
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In Molecular Biology
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In Pharmacology
Citations in the corpus
- Osteoarthritis: pathogenic signaling pathways and therapeutic targets (2023, background): “Several potential pathological mechanisms of how aging contributes to OA have been proposed recently.(41,42) The cellular senescence-associated secretory phenotype (SASP) has been detected in the degradative articular cartilage and synovial joint tissue of developing OA.”
- The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “Age-related pathology Mechanisms shared with aging process Markers References/ reviews Alzheimer’s disease Inflammation Oxidative stress Mitochondrial dysfunction Decreased proteasome activity Cellular senescence Gut microbiota alterations IL-6, TNF-α, IL-1β, TGFβ, IL-12, IL-18, and INFγ 8-hydroxygu”
- Knee osteoarthritis has doubled in prevalence since the mid-20th century (2017, background): “First, because knee OA’s prevalence increases with age (8), the rise in life expectancy in the United States since the early 20th century is thought to have led to high knee OA levels among the elderly, with the presumption that, as people age, their senescing joint tissues accumulate more wear and ”