Inflammation underlies most age-related diseases, including cancer, but the etiology is poorly understood. One proposed factor is the presence of senescent cells, which increase with age. The senescence response arrests the proliferation of potentially oncogenic cells, and most senescent cells secrete high levels of proinflammatory cytokines and other proteins. The complex senescenceassociated secretory phenotype is likely regulated at multiple levels, most of which are unknown. We show that cell surfacebound IL-1␣ is essential for signaling the senescence-associated secretion of IL-6 and IL-8, 2 proinflammatory cytokines that also reinforce the senescence growth arrest. Senescent human fibroblasts expressed high levels of IL-1␣ mRNA, intracellular protein, and cell surface-associated protein, but secreted very little protein. aging ͉ cancer ͉ inflammation ͉ invasion ͉ IRAK1