EFFECTS OF INSULIN-LIKE-GROWTH-FACTOR ADMINISTRATION AND BONE-MARROW TRANSPLANTATION ON THYMOPOIESIS IN AGED MICE

There has been considerable interest in using hormone replacement ther apy to rejuvenate the involuted thymus during aging. GH and insulin-li ke growth factor-I (IGF-I), a mediator of GH actions, have been of par ticular interest because of their thymopoietic effects and the fact th at their serum concentrations decline during aging. However, treatment of aging rodents with either GH or IGF-I does not restore thymus cell ularity to levels present in young animals, suggesting that additional defects might limit the magnitude of their effects. In particular, de ficiencies have been reported to accumulate in the bone marrow T cell precursor compartment during aging. In view of this, 18-month-old mice were administered either recombinant IGF-I, bone marrow cells from yo ung mice, or a combination of IGF-I and young bone marrow cells. Thymu s cellularity in the latter group of mice was significantly higher tha n in animals treated with hormone or bone marrow transplantation alone , suggesting that optimal therapies for restoring thymus cellularity m ust address both endocrine and hematopoietic defects that accumulate d uring aging. Results from in vitro studies using fetal thymic organ cu ltures suggest that IGF-I acts by potentiating thymic colonization by bone marrow T cell precursors and/or that the hormone affects some oth er event soon after thymus colonization.