What Do We Know About Immune System Aging from Human and Animal Studies?

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 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. Understanding the mechanisms underlying immune aging could lay the foundation for developing therapeutic strategies and lifestyle interventions to mitigate the adverse effects of this unfavorable process.