Analysis of aged wild-type and Phf6 knockout (KO) mice. (A) At 18 months of age, Phf6 KO mice had lower lymphocyte (LYMPH) counts (P = .0237; wild-type, n = 20; Phf6 KO, n = 21). (B) Aged wild-type mice had higher platelet (PLT) counts compared with aged Phf6 KO mice (P = .0002; wild-type, n = 20; Phf6 KO, n = 21). (C) Aged Phf6 KO mice had lower B220⁺ B-cell counts in their peripheral blood compared with wild-type mice (P = .0345; wild-type, n = 20; Phf6 KO, n = 21). (D) Aged Phf6 KO mice had lower CD4⁺ T-cell counts in their peripheral blood (P = .0126; wild-type, n = 20; Phf6 KO, n = 21). (E) Aged Phf6 KO mice had lower CD8⁺ T-cell counts in their peripheral blood (P = .0258; wild-type, n = 20; Phf6 KO, n = 21). (F) Aged Phf6 KO mice had larger spleens (P = .014; wild-type, n = 7; Phf6 KO, n = 10). (G) Tissue sections showed increased extramedullary hematopoiesis in the red pulp of spleens from Phf6 KO mice (inset 20×). (H) Bone marrow sections showed increased megakaryocyte number, decreased cell size, and nuclear lobation of megakaryocytes (indicated by white arrows) in Phf6 KO mice (inset 1000×; scale bar, 10 μm). (I) Megakaryocytes of aged Phf6 KO mice had decreased cell size (P = .0007; both, n = 3). (J) Aged Phf6 KO mice had increased megakaryocyte number (P = .0004; both, n = 3). (K) Aged Phf6 KO mice had higher percentages of CD4⁺ cells (left) and lower percentages of CD8⁺ cells (right) in the spleens (P = .0105 and .0247, respectively; wild-type, n = 5; Phf6 KO, n = 9). (L) In the fraction of CD4⁺ splenic T cells, Phf6 KO mice had higher percentages of naive regulatory T cells (left panel) and lower percentages of effector T cells (right panel) (P = .018 and .0205; wild-type, n = 5; Phf6 KO, n = 9). (M) In the bone marrow, aged Phf6 KO mice had decreased LT-HSCs (P = .0424; wild-type, n = 7; Phf6 KO, n = 10). *P < .05; ***P < .001. HPF, high-power field; TCRβ⁺, T-cell receptor-β⁺.