In this open access paper, the authors present their view of the role of the immune system in age-related disease. Chronic inflammation is the primary focus of many considerations of immune aging, but there are arguably many other areas of disarray and dysfunction in the aging immune system that are just as relevant to the progression of age-related disease. Like other researchers, the authors here divide the complexity of immune aging into two broad categories: inflammaging, changes that increase chronic inflammation and inappropriate immune activation, and immunosenescence, changes that weaken the efforts of immune cells to destroy pathogens and harmful cells, such as those that have become cancerous or senescent.
The proportion of elderly people is rising worldwide, especial in the developed countries. Aging-related changes in the immune system contribute to the increased susceptibility of the elderly to infectious diseases, cardiovascular disease and stroke caused by atherosclerosis, autoimmune disease such as rheumatoid arthritis, cancer, and degenerative diseases including Alzheimer's disease. Further, metabolic syndrome, which is caused by obesity, occurs from middle age, and proceeds to tissue failure such as renal failure in advanced age, is tightly related to the immune system. Chronic infections such as hepatitis induce tissue damage, which arouses immune responses and wound repair responses. Chronic inflammation follows tissue fibrosis in advanced age proceeding to tissue failure such as chronic obstructive pulmonary disease.
The most prominent cause of age-related immune dysfunction is T cell immunosenescence. There are three causes of T cell immunosenescence. One is the age-related hematopoietic stem cells (HSCs) deviation from lymphoid lineage to myeloid lineage. Second is the shrinkage of thymus. Third is expansion of T cell clones to cytomegalovirus (CMV). Changes of HSCs also affect immunosenescence. HSCs deviate to myeloid lineage by aging. Both in mice and humans the myeloid-lymphoid ratio elevates by aging, which induces the decline of lymphoid cells (T and B cells) and erythrocytes, and contributes to decline of adaptive immunity. The number of aged B cells decline and affinity and diversity of antibodies are low. Ageing related myeloid deviation increases the number of myeloid cells. However, the oxidative burst and phagocytosis of both neutrophils and macrophages are decreased. The antigen presentation of aged dendritic cells and the cytolysis of natural killer cells are low.
Pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and IL-1β are elevated in elderly people, a state that is called inflammaging, and in conjunction with obesity induce metabolic syndrome, type II diabetes, atherosclerosis, cardiac diseases. However, other reports have shown that pro-inflammatory (M1) macrophages are replaced by anti-inflammatory (M2) macrophages by aging. Here to solve this discrepancy we propose to classify age-related immune changes as follows. Age-related pathological changes are classified as firstly immune cell intrinsic changes caused by aging and secondly as the involvement of immune cells in age-related pathological changes. Increased susceptibility of the elderly to infectious diseases is mainly caused by age-related immune cell intrinsic changes, and is usually called immunosenescence. Metabolic syndrome and other related diseases, which occur at aged people, are mainly caused by immune cell attack in response to age-related tissue changes. Age-related tissue failure is then caused by repeated immune cell attack.