Senescent cells are a cause of aging, and much of the present focus in the study of cellular senescence is thus on targeting and destroying these unwanted cells in order to treat aging. However, a comparatively recent and intriguing finding is that at least some autoimmune diseases, such as type 1 diabetes, involve cellular senescence. The question at present is whether or not this true for all forms of autoimmunity.
An autoimmune condition must have a trigger, something that prompts the immune system to attack healthy tissues, and it is possible that many different triggers converge on the generation of senescent cells, with their ability to rouse the immune system to action via inflammatory secretions. Here, researchers provide evidence for cellular senescence to be involved in rheumatoid arthritis, but only in younger patients. Rheumatoid arthritis is one of the less well understood autoimmune conditions: it remains unclear as to why it occurs. It may well turn out to be several similar conditions with quite different causes, given the wide variety of patient experiences.
Tissue accumulation of senescent cells has been identified as a deleterious factor that promotes inflammation and tissue damage in different human diseases and animal models of aging related diseases. Regarding joint diseases, evidence of this concept has been only provided in human and experimental osteoarthritis (OA), with the main focus on chondrocytes and cartilage damage. Human cartilage and chondrocyte cultures from OA patients have shown increased number of senescent cells that contribute to cartilage degradation by increased IL-1, IL-6, and MMP-3 expression.
The expression of the senescence marker p16INK4a (p16) was analyzed by immunohistochemistry in rheumatoid arthritis (RA), osteoarthritis (OA), and normal synovial tissues from variably aged donors. The proportion of p16(+) senescent cells in normal synovial tissues from older donors was higher than from younger ones. Although older RA and OA synovial tissues showed proportions of senescent cells similar to older normal synovial tissues, senescence was increased in younger RA synovial tissues compared to age-matched normal synovial tissues. The percentage of senescent SA-β-gal(+) synovial fibroblasts after 14 days in culture positively correlated with donor's age.
Accumulation of senescent cells in synovial tissues increases in normal aging and prematurely in RA patients. Senescence of cultured synovial fibroblasts is accelerated upon exposure to TNFα or oxidative stress and may contribute to the pathogenesis of synovitis by increasing the production of pro-inflammatory mediators.