Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging

Abstract

Age is the most important risk factor for the development of infectious diseases, cancer and chronic inflammatory diseases including rheumatoid arthritis (RA). The very act of living causes damage to cells. A network of molecular, cellular and physiological maintenance and repair systems creates a buffering capacity against these damages. Aging leads to progressive shrinkage of the buffering capacity and increases vulnerability. In order to better understand the complex mammalian aging processes, nine hallmarks of aging and their interrelatedness were recently put forward.RA is a chronic autoimmune disease affecting the joints. Although RA may develop at a young age, the incidence of RA increases with age. It has been suggested that RA may develop as a consequence of premature aging (immunosenescence) of the immune system. Alternatively, premature aging may be the consequence of the inflammatory state in RA. In an effort to answer this chicken and egg conundrum, we here outline and discuss the nine hallmarks of aging, their contribution to the pre-aged phenotype and the effects of treatment on the reversibility of immunosenescence in RA.

When Emotional Pain Becomes Physical: Adverse Childhood Experiences, Pain, and the Role of Mood and Anxiety Disorders

“…Most pain‐related disorders tend to increase with age. Indeed, age is the most important risk factor for the development of chronic rheumatoid arthritis (Chalan et al., ). The prevalence of back and neck pain has also been found to increase with age.…”

“…Whereas the scientific study of the association between ACEs and negative health consequences, such as painful medical conditions, has expanded dramatically over the past few decades, so has the study of pain‐related medical conditions of aging . The prevalence of several pain‐related medical conditions such as arthritis, neck pain, or back pain has been found to increase with age (Chalan, van den Berg, Kroesen, Brouwer, & Boots, ; Smith, Davis, Stano, & Whedon, ). There are some unique characteristics of painful medical conditions associated with the aging process.…”

Association of Rheumatoid Factors With Subclinical and Clinical Atherosclerosis in African American Women: The Multiethnic Study of Atherosclerosis

“…The multiethnicity and sex balance in the MESA cohort make these findings more generalizable to the general population, but the older age of the participants make the findings less applicable to young populations. For example, aging is a risk factor not only for autoantibodies and RA, but also for other chronic inflammatory diseases . Prevalence of a positive RF is thought to increase with age, and there are known differences in B cell numbers and functional subsets in old age.…”

Interleukin-17 and senescence regulate the foreign body response

“…Clearance of SnCs using knockout models and senolytic drugs reduces fibrosis in idiopathic pulmonary fibrosis (IPF) and reduces inflammation and disease symptoms in arthritis, diabetes, and cardiovascular disease [21][22][23][24]. Stromal cells such as fibroblasts, endothelial cells and immune cells have all been found to undergo senescence in various tissues and disease states [25,26].…”