Although CalpTG mice exhibited less aging-related features, the lifespan was not extended in this group (Fig. 8A). Most of CalpTG mice died with an abdominal distension and autopsies revealed voluminous spleens compressing abdominal organs.Figure 8Calpastatin overexpression is associated to an increased frequency of spleen tumors. Most of CalpTG (TG) mice died with an abdominal distension due to a massive splenomegaly, there was no difference of survival rate between WT and CalpTG mice (A, n = 25/group). Among the 10 CalpTG mice sacrificed at 2 years, 7 had an apparently normal spleen but 3 were affected by splenic tumors, compressing abdominal organs (B). Aged WT mice spleens had a classical follicular architecture and white pulp containing regular lymphocytes (C, magnification ×50). Splenic architecture was disrupted in CalpTG tumoral spleens, white pulp could not be differentiated from red pulp (D, magnification ×50) and fibrosis was evident in the most severe cases (E, magnification ×50). Erythroblastic hyperplasia with evidence of dyserythropoiesis (*), and compact megacaryocytes clusters with nuclear atypia (arrows) were typical features of abnormal myeloid intrasplenic proliferation (F, magnification ×200). The partial loss of factor VIII expression by megacaryocytes (arrow) among clusters confirmed the myelodysplasic syndrome (G, magnification ×400).