The main limitation of our study is that despite clearly reduced features of aging in CalpTG mice, lifespan did not significantly differ between the 2 groups. This was due to an increased frequency of spleen tumors in calpTG mice, due to myeloid cell proliferation and fibrosis. We have previously highlighted that calpain inhibition would exert both pro and antitumoral effects in CalpTG mice32. In addition, we have evidenced that splenocytes from CalpTG mice have an increased proliferative response in vitro 11. This is a specific feature of splenocytes since calpain inhibition is usually known to decrease (or have no impact) on cell proliferation1, 5. We demonstrated that calpain inhibition amplifies IL-2 signalling via the stabilization of the IL-2 receptor γ-c common chain, providing an explanation for the proliferation response11. Interestingly, the γ-c common chain is required to activate JAK3 kinase, which has been implicated in the development of meloproliferative disorders33. One may therefore hypothesize that sustained γ-c common chain signalling would in turn promote myeloproliferative disorders. This hypothesis requires further studies including bone marrow analyses.