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Age-Associated Loss of Bone Marrow Hematopoietic Cells Is Reversed by GH and Accompanies Thymic Reconstitution

Laboratory of Immunophysiology (R.A.F., S.R.B., C.M., S.A., K.W.K.), Department of Animal Sciences, and Department of Veterinary Pathobiology (W.A.M., J.F.Z.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; and Institut National de la Recherche Agronomique-Institut National de la Santé et de la Recherche Médicale Unité 394, Unité de Recherches de Neurobiologie Intégrative (R.D.), Institute François Magendie, 33077 Bordeaux, France

Address all correspondence and requests for reprints to: Keith W. Kelley, Laboratory of Immunophysiology, University of Illinois, 207 Edward R. Madigan Laboratory, 1201 West Gregory Drive, Urbana, Illinois 61801. E-mail: kwkelley{at}uiuc.edu

Deterioration of the thymus gland during aging is accompanied by a reduction in plasma GH. Here we report gross and microscopic results from 24-month-old Wistar-Furth rats treated with rat GH derived from syngeneic GH₃ cells or with recombinant human GH. Histological evaluation of aged rats treated with either rat or human GH displayed clear morphologic evidence of thymic regeneration, reconstitution of hematopoietic cells in the bone marrow, and multiorgan extramedullary hematopoiesis. Quantitative evaluation of formalin-fixed, hematoxylin and eosin-stained sections of bone marrow from aged rats revealed at least a 50% reduction in the number hematopoietic bone marrow cells, compared with that of young 3-month-old rats. This age-associated decline in bone marrow leukocytes, as well as the increase in bone marrow adipocytes, was significantly reversed by in vivo treatment with GH. Restoration of bone marrow cellularity was caused primarily by erythrocytic and granulocytic cells, but all cell lineages were represented and their proportions were similar to those in aged control rats. On a per-cell basis, GH treatment in vivo significantly increased the number of in vitro myeloid colony forming units in both bone marrow and spleen. Morphological evidence of enhanced extramedullary hematopoiesis was observed in the spleen, liver, and adrenal glands from animals treated with GH. These results confirm that GH prevents thymic aging. Furthermore, these data significantly extend earlier findings by establishing that GH dramatically promotes reconstitution of another primary hematopoietic tissue by reversing the accumulation of bone marrow adipocytes and by restoring the number of bone marrow myeloid cells of both the erythrocytic and granulocytic lineages.

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