Transplantation of old Polg^A marrow into young Polg⁺ recipients accelerates the development of age-related macrocytic anemia and leukopenia and induces dysfunction in splenic mitochondria. Two-month-old B6.SJL hosts were lethally irradiated and then reconstituted with 5 × 10⁶ nucleated marrow cells from 8-month-old donor mice. Peripheral-blood samples were analyzed as in Figure 1 from 1 to 6 months after transplantation (3-8 months of age and 9-14 months of marrow age). Each point represents the mean ± SEM of recipients of Polg⁺ marrow (n = 5, solid lines) and recipients of Polg^A marrow (n = 5, dotted lines). (A) Hemoglobin levels. (B) Mean corpuscular volume of all RBCs (□) and of reticulocytes only (◇). (C) Platelet count. (D) White blood cell (WBC) count. (E) Representative Wright-Giemsa stained images of RBCs and lymphocytes from peripheral blood smears of 5-month-old transplant recipients (11 months marrow age). Bars represent 10 microns. (F) The relative activity of the mtDNA-dependent mitochondrial enzyme COX was compared with that of the nuclear DNA-dependent mitochondrial enzyme CS in mitochondria isolated from the livers and spleens of Polg⁺ transplanted with either Polg⁺ or Polg^A bone marrow. Each bar represents the mean ± SEM of mitochondria isolated from liver or spleen, respectively, of mice transplanted with Polg⁺ marrow (n = 6, cross-hatched) and Polg^A marrow (n = 3, solid gray). **P < .01 (statistical significance) by Student t test; ns, nonsignificant.