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Whether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1 mice were studied at ages 3, 13, or 27-28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43% vs 49% (p less than .001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20-25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with 59Fe. 59Fe was given following the second bleed, and 1 day later RBC 59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal-appearing hair; the latter was subdivided into those weighing less (25-26 g) or more (30-34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild "dilutional" anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine aging process.

Distribution of 59Fe into various bone groups of the complete murine skeleton was studied using two methods of dividing up the bones: 1) our previously reported technique of simply cutting up a skinned, eviscerated carcass and 2) separating bones from skeletons cleaned of overlying tissue by beetles, Dermestes species. The total percentage of injected 59Fe recovered in the sum of all skeletal parts, the percentage of total skeletal 59Fe found in each bone group, and the overall accuracy of determining these values were quite similar for the two techniques. The only statistically significant difference shown was a modest decrease in the percentage of total skeletal iron found in ribs plus sternum plus cervical and thoracic spine in beetle-cleaned as compared to cut up groups and we would not consider this to be of biological significance. Cutting up carcasses is the simpler of the two techniques but there are circumstances in which beetle digestion would be advantageous. In addition, we collected data on the reproducibility and precision of determining the percentage of 59Fe injected which is found in a "pulled off" foreleg plus scapula and of the distribution of 59Fe within three cut up pieces from the leg and within the scapula. These data can be used as a measure of overall changes in marrow mass and/or distribution, or at least they can be used as a screening procedure to detect such. This simple procedure adds potentially useful values for fully interpreting hematopoietic changes in the mouse.

Electronic sizing with a Coulter Counter was used to measure the frequency and number of cells with a large nuclear volume in tissues from AKR/J mice with spontaneous, long passaged, or first passage leukemia. The mean percentage of cells with a large nuclear volume was 1% in the blood, 4% in the spleen, 10% in the bone marrow, and 5% in the thymus of nonleukemic AKR/J mice. The percentage of cells with a large nucleus increased to 14-83% in all four tissues from AKR/J mice with spontaneous leukemia. In mice with a long passaged leukemia, a progressive increase in the percentage of cells with a large nucleus in the spleen and blood was associated with an increase in the number of cells/tissue with a large nucleus. However, in the bone marrow, an increase in percentage of cells with a large nuclear volume appeared to be the result of a decrease in the number of cells/humerus with a small nuclear volume. In the thymus, there was only a slight increase in the percentage of cells with a large nucleus. In mice with a first passage leukemia, there was a progressive increase, until death of the animals (21 +/- 1.9 days), in thymus weight and in the percentage of cells with a large nucleus. Also, the number of cells with a large nucleus increased in the spleen and bone marrow until day 12. Thereafter, there was a decrease in the total number of cells and number of cells with a large nucleus.