The dynamic of senescent cells accumulation can explain the age-specific incidence of autoimmune diseases

Abstract

Autoimmune diseases arise when the immune system turns against normal components of the body. Overwhelming evidence indicate that the immune system deteriorates with age. The mechanism that leads to autoimmunity is complex and not fully understood, and in many cases there is no effective therapy. Another process related to aging is the accumulation of senescent cells. These cells are considered to confer deleterious effects, including the promotion of organismal aging and age-related pathologies. We hypothesize that autoimmune diseases are caused by two age related process: (1) different rate of senescent cells accumulation in the immune system and target tissue/organ, (2) heterogeneous accumulation of senescent cells in tissues/organs. Separately or combined, these two processes are at the base of autoimmune diseases. If the hypothesis is correct, the control of the formation, accumulation and elimination of senescent cells can be used to prevent and/or treat autoimmune diseases. The accumulation or removal of senescent cells would modify the microenvironment and therefore the immune reaction. Many other problems caused by immunosenescence can be also partially explained by our hypothesis. Basically, the accumulation of senescent cells is a finely regulated process. Every imbalance in the accumulation of senescent cells between the immune system and the potential target organs can initiate a chronic inflammation or autoimmunity.