Dr. Weksler's research focuses on the mechanisms underlying the aging process, in general, and the age-associated changes in the immune system in particular. The laboratory studies the effect of age on the immune system of humans and experimental animals. Specifically, we are interested in the molecular and cellular basis for the age-associated dysregulation of the immune system and the contributions of these changes to the increased risk of the elderly to infection and neoplastic disease. Thymic involution appears to be the pacesetter of immune senescence and directly affects the generation and function of T lymphocytes. Indirectly, impaired T cell function compromises the generation of B cells and their production of antibodies. The impaired production of IL-16 by T cells from old mice explains, at least in part, the decreased expression of RAG genes and the consequent impaired rearrangement of the immunoglobulin gene segments in bone marrow B cell precursors which leads to apoptosis of Pre-B cells in the bone marrow. Recently, we have detected the appearance of monoclonal B and T cell in both elderly humans and old mice. The relationship of these "benign" clonal expansions to late-life leukemia and lymphoma is under study.