Should We Think of Rheumatoid Arthritis as an Age-Related Condition?
There are medical conditions that occur only in old age, and there are medical conditions, such as cancer, that can occur at any point in life, but more so in the old. Then there are grey area conditions that may occur to some greater degree in later life, or be worse in later life, but this is by no means widely appreciated. Where does the autoimmune condition of rheumatoid arthritis sit in this spectrum? Unlike cancer, it is not commonly thought of as an age-related disease, even though it is certainly affected and made worse by the processes of aging. This point is discussed in today's open access commentary and the paper to which it refers.
One of the more interesting aspects of this work is the background of poor mechanistic understanding that attends research into the treatment of rheumatoid arthritis. Despite considerable effort, it remains a poorly understood condition. The immune system is complex, and there as, as of yet, no very straightforward evidence for a specific malfunction of the immune system to trigger the condition. Available treatments take the form of quite blunt approaches to the suppression of chronic inflammatory dysfunction of the immune system, such as TNFα inhibition, and have meaningful long-term side-effects related to impairment of the necessary immune response to infection and damage.
Biological ageing: a promising target for prevention and management of rheumatoid arthritis
Researchers have used US National Health and Nutrition Examination Survey and UK Biobank to show that people with accelerated biological ageing had an increased risk of rheumatoid arthritis compared with people without accelerated biological ageing. Accelerated biological ageing particularly increased the risk among people with a high genetic predisposition for rheumatoid arthritis, suggesting a joint effect on the risk of incident disease. The life expectancy at age 45 years of people with both rheumatoid arthritis and accelerated biological ageing was 2.4-5.7 years lower than that of people with rheumatoid arthritis who did not have accelerated biological ageing. The findings support the significant effects of biological ageing on the development and progression of rheumatoid arthritis.
The pathogenesis of accelerated biological ageing in rheumatoid arthritis is complex and not fully understood. The high prevalence of comorbidities and associated polypharmacy in rheumatoid arthritis is a potential pathway by which biological ageing is accelerated and life expectancy is reduced. Besides the genetic factors associated with rheumatoid arthritis, molecular mechanisms, including epigenetic modifications and telomere attrition, are interrelated with biological ageing and thus might increase susceptibility to rheumatoid arthritis. Regarding immune ageing, T cells are particularly susceptible to ageing-related changes. Treatment with biological and targeted synthetic disease-modifying antirheumatics might be effective in restoring the functional intactness of aging T cells in rheumatoid arthritis. Since the advent of these drugs, life expectancy and quality of life have increased in patients with rheumatoid arthritis. Whether these drugs have a favourable effect on biological ageing in rheumatoid arthritis should be investigated.
Life expectancy is a key indicator reflecting the mortality associated with a disease. Diverging from previous research that primarily focused on the effects of novel treatments, this study has shifted attention to an important and potentially reversible factor: loss of life expectancy resulting from accelerated biological ageing. Notably, the authors found that the absolute loss in life expectancy attributed to ageing characteristics did not differ significantly across age groups. These results suggest that the effects of reducing or reversing accelerated biological ageing on increasing life expectancy could be similar across different age groups, highlighting the importance of management of biological ageing at every life stage. Thus, controlling biological ageing could be an effective way to enhance quality of life and extend the lifespan of people with rheumatoid arthritis, irrespective of chronological age. However, given that rheumatoid arthritis primarily affects women and the inherent sex-based differences in life expectancy and in the speeds and processes of ageing, it remains unclear whether accelerated biological ageing affects life expectancy differently for men and for women with rheumatoid arthritis. Therefore further investigation is needed.