We previously described that calpains promote the development of inflammatory and fibrotic lesions in kidney and arteries in response to angiotensin II, and that calpastatin overexpression protected mice against these lesions10. Interestingly, angiotensin II, through AT-1 receptor signalling, promotes vascular aging12. Moreover, calpains are potent mediators of neurological diseases, including Alzheimer disease13, 14. A specific feature of tissue aging is the development of an inflammatory phenotype, including overexpression of innate immunity and inflammasome-related cytokines, so-called “inflammaging”15. Although its expression is weak and difficult to assess in vivo, one of the main cytokine linked to inflammaging is interleukin-1α (IL-1α)16. It was therefore tempting to speculate that calpains would promote vascular and kidney aging. At last, proteomic analysis performed in Klotho-invalidated mice revealed that in the absence of Klotho, the main anti-aging mechanism identified to date, alpha-spectrin clivage was strongly increased. Further analyses identified that this clivage was specific to calpains, evidencing thereby that Klotho may decrease calpain activity17.