Pathophysiologic aging-related changes in the hematopoietic systems in ATM and TERT doubly null mice. (A) H&E staining of sections of decalcified femur, near the proximal metaphysis, from young mice (12 weeks of age: top) and aged mice (36 weeks of age: bottom). Progression of hypoplastic fatty marrow is apparent in aged TERT^−/− mice, and significantly further progression in aged ATM^−/−TERT^−/− mice, and is absent in young mice. (B) The numbers of CD150⁺ CD41⁻ CD48⁻ LSKs and CD34⁻ LSKs from ATM^−/−TERT^−/− mice are increased compared with those of other genotypes. Relative numbers of the indicated fractions of BM cells from young (11 weeks of age: top) and aged (37 weeks of age: bottom) WT (white bar), TERT^−/− (light-gray bar), ATM^−/− (dark-gray bar), or ATM^−/−TERT^−/− (black bar) mice (left). Representative FACS analyses of BM-MNCs in aged mice are also shown (right). Total cell numbers of indicated populations are compensated with body weight of each mouse and data shown are frequencies relative to those of WT, with each value representing the mean ± SD of 3 experiments (*P < .05). (C) Myeloid shift is observed in the BM of TERT^−/−, ATM^−/−, and ATM^−/−TERT^−/− mice. The shift is most obvious in ATM^−/−TERT^−/− mice and is also greater in aged mice (38 weeks of age: bottom) than in young mice (12 weeks of age: top). Frequency of each lineage (expressed as a percentage of WT: left) and representative FACS patterns of B-cell lineage and myeloid lineage (right) are shown for the indicated genotypes (*P < .05, **P < .01, n = 3).