Age-dependent role of histone deacetylase Sirt7 on haematopoiesis

Sirt7 is a member of the sirtuin family of proteins, which are NAD+-dependent deacetylases and ADP-ribosyltransferases. It is involved in a wide range of cellular processes. To study the specific role of Sirt7 in hematopoiesis during aging, the gene was specifically inactivated in hematopoietic stem cells (HSC). Vav1 promoter mediated expression of CRE recombinase in floxed Sirt7 mice resulted in specific inactivation of Sirt7 in the hematopoietic stem and progenitor cells. Young mice exhibited a normal peripheral blood count and no detectable hematological aberrancies. Peripheral blood of 19-month-old Sirt7 knockout mice revealed a diminished abundance of lymphocytes, but elevated count of monocytes compared to control mice. The number of erythrocytes, platelets, and hemoglobin concentration remained unchanged. In the bone marrow of aged mice, a reduced abundance of myeloid undifferentiated cells could be observed. The development of hepatomegaly due to Sirt7 gene inactivation could indicate a myeloproliferative influence. Taken together, our data demonstrate that Sirt7 functions as a critical suppressor on hematopoietic stem cells differentiation in aged mice.