Reviewing What is Known of the Aging of the Immune System
The immune system and its supporting organs and structures throughout the body, such as bone marrow, spleen, lymphatic system, and thymus, are collectively make up a very complex system. The way in which the immune system ages is thus also very complex. Different specialized cell populations change in number and function. Immune cells are influenced into maladative inflammatory behavior by some combination of internal molecular damage and disarray on the one hand coupled with external damage to tissue on the other. The supply of many types of immune cell is much reduced from youthful levels, allowing malfunctioning and senescent immune cells to accumulate. The immune system is crucial to health, not just as a defense against pathogens and potentially cancerous cells, but also due to its role in day to day tissue maintenance. Improving immune function in older people is likely to produce meaningful benefits. There are certainly many, many distinct issues to provide starting points for those who wish to develop novel therapies with that goal in mind.
Aging is accompanied by complex structural and functional immune system changes driven by genomic instability, epigenetic alterations, mitochondrial dysfunction, telomere attrition, loss of proteostasis, deregulated nutrient sensing, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype, which altogether lead to severe consequences including altered antimicrobial defense, the overproduction of autoantibodies, and chronic, low-grade inflammation (inflammaging).
In this article, we summarize age-related alterations in the function of primary and secondary lymphoid organs, including the bone marrow, thymus, spleen, and lymph nodes. The involution of these organs leads to impaired hematopoiesis, reduced production of naïve lymphocytes, and immune microenvironment disruption. We also describe aging-related impairment of the activity of neutrophils, macrophages, dendritic cells, and natural killer cells, as well as dysregulation of T lymphocyte and B lymphocyte responses. Specifically, these alterations include a decline in naïve cell populations, an accumulation of memory and exhausted cells, and a reduction in the diversity of antigen receptors. Consequently, older individuals exhibit increased susceptibility to infections, cancer, and autoimmune diseases, along with diminished vaccine efficacy.