Targets of immune regeneration in rheumatoid arthritis

Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the process of immune aging at the center of aging biology. Immune aging affects individuals older than 50 years and is accelerated in patients with the autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline in protective immune responses and a parallel increase in tissue inflammatory responses. By studying immune cells in patients with rheumatoid arthritis, several of the molecular underpinnings of the immune aging process have been delineated, such as the loss of telomeres and inefficiencies in the repair of damaged DNA. Aging T cells display a series of abnormalities, including the unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic competence, that alter their response to stimulating signals and undermine their longevity. Understanding the connection between accelerated immune aging and autoimmunity remains an area of active research. With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging.