An interesting fact about the adaptive immune system: the number of T cells in the body remains much the same across the entire lifespan, even after the supply of new T cells all but ceases in middle age. T cells are created as thymocytes by hematopoietic cells in the bone marrow, and then mature in the thymus. The supply of new cells from the bone marrow is negatively affected by age, while the thymus atrophies, active tissue becoming replaced with fat. Lacking replacements, the T cell population in the body becomes increasingly exhausted, senescent, and otherwise damaged. Many T cells become inappropriately specialized to persistent viral infections such as cytomegalovirus, leaving too few naive T cells to tackle new threats. Harmful subpopulations of T cell arise, connected with chronic inflammation, autoimmunity, and tissue dysfunction. The aging of the immune system is an important component of age-related degeneration.
The adaptive immune system has the enormous challenge to protect the host through the generation and differentiation of pathogen-specific short-lived effector T cells while in parallel developing long-lived memory cells to control future encounters with the same pathogen. A complex regulatory network is needed to preserve a population of naïve cells over lifetime that exhibit sufficient diversity of antigen receptors to respond to new antigens, while also sustaining immune memory. In parallel, cells need to maintain their proliferative potential and the plasticity to differentiate into different functional lineages.
Initial signs of waning immune competence emerge after 50 years of age, with increasing clinical relevance in the 7th -10th decade of life. Morbidity and mortality from infections increase, as drastically exemplified by the current COVID-19 pandemic. Many vaccines, such as for the influenza virus, are poorly effective to generate protective immunity in older individuals. Age-associated changes occur at the level of the T cell population as well as the functionality of its cellular constituents. The system highly relies on the self-renewal of naïve and memory T cells, which is robust but eventually fails. Genetic and epigenetic modifications contribute to functional differences in responsiveness and differentiation potential.
To some extent, these changes arise from defective maintenance; to some, they represent successful, but not universally beneficial adaptations to the aging host. Interventions that can compensate for the age-related defects and improve immune responses in older adults are increasingly within reach.