Autoimmunity as a model for aging: insight into their similar mechanisms

Abstract

The age-related decline of immunologic function is generally associated with an increase in susceptibility to infections and in incidence of autoimmune phenomena and malignancies in elderly individuals. We found that circulating B lymphocytes from elderly individuals contained reduced numbers of genuine resting B cells and increased numbers of B cells that spontaneously secrete immunoglobulins, suggesting polyclonal B cell activation in vivo in elderly individuals. It is well known that the prevalence rate of rheumatoid factors and antinuclear antibodies in circulation correlates well with aging. It has also been reported that MRL +/+ mice, a counterpart of MRL lpr/lpr mice, that spontaneously produce antinuclear autoantibodies are predisposed to hypermaturity and accelerated aging. Recently, it was also reported that autoreactive T cells are prevalent in the aged mice and that T helper (T_h) 1 cytokine production such as interferon (IFN)-γ and interleukin (IL)-2 was significantly decreased, whereas T_h2 cytokines production including IL-4 and IL-6 was unchanged or up-regulated in the elderly humans. This imbalance of T_h1/T_h2 may be important for both aged individuals and patients with autoimmune diseases. In addition, these changes associated with aging may be partly due to the alteration of neuro-endocrine systems. Although autoimmunity is considered to be physiological phenomenon and requires additional factor(s) for the development of autoimmune diseases, it should be emphasized that alterations of the immune system with aging resemble autoimmunity and autoimmune diseases.

Key words::

• aging
• autoimmunity
• autoantibody
• T_h1/T_h2