Pharmacological Modulation of Immunosenescence and Inflammaging: Senolytics, Senomorphics, and Emerging Therapies.
BACKGROUND Ageing is a major risk factor for chronic inflammatory and immune-mediated diseases and is characterised by progressive immune dysfunction. This process, termed immunosenescence, affects both innate and adaptive immunity, resulting in reduced naïve T and B cell production, accumulation of senescent immune cells, impaired pathogen recognition, and weakened immune surveillance. These changes are accompanied by a persistent, low-grade inflammatory state known as inflammaging, which occurs even in the absence of infection and contributes to increased susceptibility to infections, poor vaccine responses, and age-related disorders. METHODS This review integrates evidence from basic, translational, and clinical studies to elucidate the molecular and cellular mechanisms linking immunosenescence and inflammaging, with a focus on immune cell alterations and the role of senescent cells and their secretory phenotype. RESULTS Accumulation of senescent cells and the senescence-associated secretory phenotype (SASP) play a central role in sustaining chronic inflammation and disrupting tissue homeostasis. These processes impair immune function and tissue repair, increasing vulnerability to disease. Emerging therapeutic strategies, including senolytics, senomorphics, metabolic modulators, repurposed drugs, and microbiome-targeted interventions such as postbiotics, show potential in modulating these pathways. CONCLUSION Immunosenescence and inflammaging are closely interconnected drivers of age-related disease. Targeting senescent cells and inflammatory signalling pathways may offer promising strategies to restore immune resilience, reduce chronic inflammation, and promote healthy ageing. Further research is required to translate these approaches into clinical practice.