Immune system deterioration in the elderly, commonly believed to be a primary function of thymus gland shriveling with age, has now been linked to aging bone marrow cells as well. This finding of Prof. Amiela Globerson of the Institute's Department of Cell Biology indicates that rather than independently governing immune system decline, the thymus is itself influenced by the aging of the bone marrow cells it is charged with nursing. This knowledge may advance the ongoing search for techniques to bolster immune system function in the elderly.
Since the thymus is a major site for the maturation of T lymphocytes white blood cells concerned with immunity to infection and protection against cancer the shriveling of the gland has been commonly implicated in the weakening of the body's immune response with age. These lymphocytes develop from stem cells that originate in bone marrow and then travel to the thymus; there they mature and receive "training" in the recognition of foreign invaders and in avoiding reactions against the body's self-constituents.
Prof. Globerson has now found that the influence is mutual: the bone marrow cells not only are nurtured by the thymus, but regulate thymus tissue function as well. She demonstrated that aged bone marrow cells are unable to develop fully in the thymus, or to convey proper signals to the gland. This implies that efforts to retard immune system degeneration should focus not only on the thymus gland but on aging processes in the bone marrow as well.
Globerson exposed fetal thymus tissue culture to radiation, thereby destroying the T cells while leaving the "stroma" the organ-tissue constituents intact. She then inserted stem cells from young animals into some of the thymus stromas, and stem cells from old animas into others. The old cells were found to undergo less clonal expansion and produce far fewer T cells than the younger cells. Therefore, the aging of stem cells is likely to play a major role in declining immune system function.
Prof. Globerson holds the Harold S. And Harriet B. Brady Chair of Cancer Research