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Immune system stimulation and oxidative stress exposure occurring over the course of life promote a state called inflammaging; that is, inflammation associated with aging. This low-grade inflammation status is associated with almost all the health problems typical of aging, including cancer. It is due to chronic immune system stimulation, which induces the increase of both activated immune cells and pro-inflammatory lymphokine production, contributing to the imbalance between inflammatory and anti-inflammatory mechanisms. Moreover, during the course of life, oxidative stress damages cell lipids, proteins, and nucleic acids, triggering protective mechanisms; however, as oxidative insult progresses, such protective mechanisms become less effective. The consequent accumulation of senescent, dysfunctional, and mutated cells leads to a reduction in the immune response and to an increased risk of cancer.

Besides the increased tendency for inflammation, aging also comes with immune defense decay. This phenomenon, known as immunosenescence, is associated with the reduction of the adaptive immune response, the enhancement of the susceptibility to infections, the increase in the production of autoantibodies (that is, antibodies directed against structures of the organism), and increased mortality. This may explain why some diseases involving the immune system (such as malignancies) develop during aging.

Actually, the immune system is thought to play an active role in aging, and physiological events such as the involution of thymus gland (which in the first years of life participates in immune cell maturation) support this theory. In general, the ability of constantly renewing immune system cells declines with age, and the hematopoietic tissue that produces them decreases.

The aging of the immune system compromises health span, that is the period of life free from chronic diseases and disability. In fact, immunosenescence reduces the ability to respond to new antigens (with the accumulation of memory T cells) and this inflammaging is associated with several health risks. However, aging differs from one individual to another, and the hallmarks of immunosenescence are affected by the history of individual’s exposure to pathogens.

Thymus involution starts early in life and is nearly completed between 40 and 50 years old. Both innate (e.g. monocytes and Natural Killer – NK – cells, which provide a fast protection, representing body’s first line of defense) and adaptive immune response (whose cells – T and B cells – respond to the inflammatory environment generated by the innate immunity, proliferating and differentiating to eliminate the health insult) progressively decrease during aging, with a significant decrease in the absolute frequencies of CD45+ Peripheral Blood Mononuclear Cells (PBMCs, including lymphocytes and monocytes).

However, adaptive immunity is more extensively affected. Its effectiveness diminishes because of changes in both the quality and the quantity of the T and B cell responses. Consequentially, the reaction against newly encountered antigens becomes inadequate, and older individuals are more susceptible to the development of age-related diseases, including cancer.