immunosenescence

Immunosenescence refers to the gradual deterioration of the immune system that occurs with advancing age. It involves coordinated changes in both the innate and adaptive immune branches that collectively reduce the ability to respond to infections and vaccines while increasing baseline inflammation in the elderly.

Thymic involution reduces production of naive T cells, while existing T cells accumulate memory and senescent phenotypes with limited proliferative capacity. The B cell compartment shows reduced production and repertoire diversity, leading to weaker responses to new antigens and vaccines. Innate immune cells, including macrophages and neutrophils, may exhibit altered signaling, impaired phagocytosis, and diminished responsiveness. A chronic, low-grade inflammatory state known as inflammaging is common in older adults and is associated with elevated cytokines such as IL-6 and TNF-α.

These changes contribute to increased susceptibility to infections (notably influenza and pneumococcal disease), reduced vaccine efficacy, slower pathogen clearance, and a higher risk of cancer and autoimmune phenomena. The extent of immunosenescence varies between individuals and is influenced by genetic factors, sex, nutrition, physical activity, comorbidities, and prior infections.

Preventive and therapeutic approaches focus on improving vaccination outcomes and overall health status, including age-appropriate vaccines and optimized booster schedules, as well as lifestyle interventions. Research explores strategies to slow or reverse immune aging, such as targeted vaccines, cytokine modulation, and immune system rejuvenation therapies, though many remain experimental.