Alterations in Bone Marrow Stroma with Aging (36.5)

Abstract B lymphopoiesis arrests in rabbits by 16 weeks of age, and data suggest that the bone marrow (BM) environment is responsible for this. We hypothesize that this arrest is due to differences in the BM stroma of young and adult rabbits. Using limiting dilution analysis to quantify the number of CFU in BM of 2 to 6 wk-old rabbits, we found an 8-10 fold decrease in the number of stromal progenitors by 6 wk-of-age. This decrease in stromal progenitors is reflective of the age-related decline in progenitor B cells in BM. Histology of BM sections reveals trabecular bone formation in young rabbits but not in adults; in contrast, BM from adults shows large amounts of adipose tissue. We tested the capability of stromal progenitors to differentiate into adipocytes or osteoblasts in vitro , and found that stromal progenitors from BM of young rabbits displayed a higher propensity to form oseoblastic colonies than do stromal progenitors from BM of adults, which more readily formed adipocytic colonies. We conclude that with aging, the number of BM stromal progenitors decreases dramatically, and further, that these progenitors from adults more readily differentiate into adipocytes than into osteoblasts. We suggest that these changes in BM are responsible for the arrest of B lymphopoiesis.