Immunological tolerance to self-antigen is mediated by deletion of self-reactive lymphocytes by apoptosis, unresponsiveness to self-antigens (anergy), regulation by T cells (Treg), and efficient removal of apoptotic bodies by phagocytic cells. Dendritic cells (DCs) play an important role in both tolerance (predominantly via induction of Treg) and inthe induction of immune response to non-self antigens. Therefore, an impairment of DCs functions may result in the loss of tolerance and induction of immune response to self-antigens, resulting in autoimmunity. Aging represents a paradox of impaired response to non-self antigens, and an increased response to self-antigens, resulting in an increased susceptibility to infections, and development of autoimmunity in aged humans. I have reviewed the role of DCs and mechanisms involved in autoimmunity, including epigenetic changes in aged DNA, and histone modifications in chromatin in human aging.