Immunosenescence in Older Patients with Psoriasis: Mechanistic Insights and Opportunities for Biologic Therapy

Psoriasis is a chronic systemic inflammatory disease that is increasingly seen in older patients. As the immune system ages, the mechanisms that normally keep immune responses in balance become less precise. The adaptive immune system is reshaped both quantitatively and structurally, whereas innate immunity becomes less well regulated rather than simply less active. Age-related changes in the skin microenvironment may also help sustain local inflammatory signaling. In older patients with psoriasis, these age-related immune changes intersect with the pathways already known to drive disease. Th17 and cytotoxic CD8⁺ T (Tc17) responses remain prominent, control of antigen-presenting cells (APCs) is less tightly regulated, and natural killer (NK) cell function is also altered. These changes help sustain inflammation and further compromise the epidermal barrier. Treatment decisions are made more complex by common comorbidities, especially cardiovascular disease and metabolic syndrome. Biologic agents targeting TNF-α, IL-12/23, IL-23, IL-17, and IL-36 have markedly expanded the therapeutic options for psoriasis. Direct evidence in older patients with psoriasis remains limited, but the studies available so far suggest that treatment efficacy is broadly comparable to that seen in younger populations. Even so, immune aging may still affect both susceptibility to infection and the likelihood of remaining on treatment over time. TNF inhibitors remain particularly useful in patients with systemic inflammatory comorbidities, although infection risk requires close attention. IL-12/23 inhibitors offer the advantage of dual cytokine blockade. Selective IL-23 inhibitors allow more focused control of Th17-driven inflammation while leaving Th1 function relatively preserved. IL-17 inhibitors are often associated with rapid clinical improvement, whereas IL-36 inhibitors may be particularly promising in pustular disease. Clarifying how immunosenescence shapes disease behavior and treatment response in older patients should make it easier to individualize therapy.