Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities

Aging is increasingly viewed as an organism-wide process marked by systemic decline and multimorbidity. This Review frames immunosenescence as a context-dependent mediator, amplifier, or consequence of multi-organ dysfunction, integrating niche-centered mechanisms, bidirectional immune–organ interactions, innate–adaptive remodeling, immune–tissue axes, and multidimensional biomarkers. We also highlight current limitations, including context heterogeneity and unresolved causality, and discuss senolytic, senomorphic, and other therapeutic strategies with potential relevance and limitations for healthspan extension.