Does the immune system grow old gracefully?

T cells represent a key component of the immune system; they are able to directly remove pathogens as well as coordinate other elements of the immune system to elicit their function. A large number of studies have suggested that a progressive decline in T cell function is one of the major factors that contributes to the clinical features of immunosenescence. T cells are derived from haematopietic stem cells (HSCs), however for HSCs to become T cells they are required to enter the thymus (a primary lymphoid organ) and in the presence of appropriate signals, provided by the thymic environment, differentiate into T cells. Moreover, the thymus is solely responsible for producing T cells, such that failure to generate the thymus leads to the absence of T cells in the peripheral circulation (i.e., the entire vascular system). Involution is a general term for the shrinkage of an organ in old age, or due to inactivity (e.g., post-birth reduction in the size of the uterus). Age-associated thymic involution (Figure 2) is one of the most recognizable features of the aging immune system. This regression of the thymus is associated with a reduction in tissue mass, loss of tissue structure and a decline in the number of thymocytes (T cell precursors). Ultimately, this leads to a reduced production of new (naive) T cells, the consequence of which has major ramifications on functional immunity. Why the thymus involutes with age is still unclear. One suggestion is that thymocyte development is highly energy demanding and once the T cell pool is established (as T cells are long-lived), the thymus regresses, so that energy can be redirected to other cellular systems. Nevertheless, this process occurs in all species that possess a thymus, which not only indicates that age-associated involution is an evolutionary-conserved event, but also makes it a suitable biomarker of aging. The start of thymic involution is believed to occur during adolescence; however, there is significant evidence to suggest it may occur earlier in life. Furthermore, thymic activity does not decline at a steady rate, but instead appears to be phasic (Figure 2). The onset of thymic involution appears to be relative to the lifespan of The immune system consists of an array of cells and soluble factors that are designed to protect the host from pathogens and infectious diseases, and therefore represents a vital entity for an organism’s survival. Moreover, with increasing age, the immune system undergoes dramatic changes resulting in a decline in immune function, which is seen in humans as well as in many other species. Such changes, collectively termed immunosenescence, often lead to increased susceptibility and severity of infections, cancers and autoimmune diseases, together with the reduced ability to respond to vaccination, which is often seen in older individuals. Given the direct correlation between immune function and health, the increased morbidity and mortality seen in older individuals following infection are due, in large part, to the age-associated changes in the immune system. This is of great concern since, according to the Office of National Statistics, the population of individuals over the age of 65 in the UK is steadily increasing, standing at 18.2% in mid-2017 and estimated to rise to 20.7% by 2027 and 24% by 2037 (Figure 1); a trend that is also seen globally. Although this area of research is relatively new in comparison to other fields of immunology, investigations have identified several differences between the young and aged immune system which has helped shed light on the possible mechanisms associated with immunosenescence. ‘You don’t stop laughing when you grow old, you grow old when you stop laughing’. George Bernard Shaw