Immunology and Antiaging Medicine: What Is Immunosenescence?

The immune system is a biological function with a complex network of cells and tissues essential for maintaining the health of our bodies. Characteristic changes with aging include ① increased susceptibility and severity due to decreased body defense ability against pathogens and response to vaccination, ② enhanced autoimmune reactions causing tissue damage, ③ accumulation of damage-associated molecular patterns (DAMPs) in the body, and decreased immune surveillance ability to monitor and remove aging cells and cancer cells, leading to disease onset and chronic inflammation. The decline in function with aging is more susceptible in the acquired immune system, which is centered on antigen-specific immune memory of T cells and B cells, compared to the innate immune system, which primarily eliminates pathogens through phagocytosis and associated inflammatory reactions. Immunosenescence is a phenomenon where multifaceted declines in immune function are observed with aging, and understanding and elucidating the mechanisms of its control are attracting attention due to its deep connection with extending healthy lifespan in an aging society. In fact, about 95% of annual deaths from seasonal influenza are elderly people aged 65 and over, and the severity and mortality rate of elderly people who have contracted infectious diseases caused by foreign pathogens, such as the recent COVID-19, are extremely high, which is a serious situation considering the decline in immune function against pathogens with aging. On the other hand, the function to distinguish self from non-self also decreases with aging, not only making the immune response fragile because foreign pathogens cannot be recognized as non-self, but also causing autoimmune diseases by attacking self-antigens with their own immune system, which is common in the elderly. Here, instead of summarizing the multifaceted aging changes that cause immunosenescence at the individual immune cell level, which have been clarified so far, we would like to discuss the contribution and role of cellular aging in immunosenescence at the immune tissue or individual level from the perspective of cellular aging and tissue aging research, which has been making remarkable progress in recent years.