As a conclusion, we have evidenced that calpains are a key mediator of inflammaging, especially in the kidney tissue, and that their long-term specific inhibition decreases the impact of aging, markers of senescence and inflammaging mediators. Among the mechanisms involved, SASP-related cytokines production is clearly impacted by calpain inhibition. These results highlight the deleterious role of inflammaging in kidney and vascular lesions occurring with aging.