Immunosenescence and Allergy: Molecular and Cellular Links Between Inflammaging, Neuro-Immune Aging, and Response to Biologic Therapies

With the global increase in population aging, allergic diseases in older adults are becoming an increasingly relevant clinical and public health challenge. Age-related molecular and cellular alterations significantly affect the pathophysiology, clinical manifestations, diagnosis, and management of major allergic diseases in the elderly. This review focuses on immunosenescence in major allergic conditions, including asthma, chronic urticaria and angioedema, dermatitis, food and drug allergies, and hymenoptera venom hypersensitivity. Particular emphasis is placed on molecular mechanisms underlying immune aging, such as inflammaging, dysregulation of innate and adaptive immune responses, epithelial barrier dysfunction, microbiota alterations, neuro-immune interactions, and age-related comorbidities. Sex-related differences in immune responses are also addressed, together with current diagnostic and therapeutic strategies, including the opportunities and limitations of biologic therapies in aging populations. Despite growing interest in this field, a major limitation remains the paucity of studies specifically targeting geriatric populations, underscoring the need for age- and sex-specific research and dedicated clinical trials. A personalized approach integrating frailty assessment and immune profiling is essential to optimize the management of allergic diseases in older adults.