UNDERSTANDING THE MECHANISM OF THE AGE-CHANGE OF THYMIC FUNCTION TO PROMOTE T-CELL DIFFERENTIATION

Immunological functions peak at around puberty and gradually decline t hereafter with advancing age. The immunological decline mainly occurs in the T cell-dependent immune system and is generally associated with an increase in not only susceptibility to infections but also inciden ce of autoimmune phenomena. The age-related changes in T-cell dependen t immune functions can be mainly ascribed to the physiological thymic involution which starts in the early phase of life. The age-related th ymic involution can be ascribed to either extrinsic or intrinsic facto rs. Bone marrow stem cells can be one of the extrinsic factors for the thymic involution, but their role is estimated to be marginal as comp ared with alteration of the thymic microenvironment. With advancing ag e, the thymic capacity to promote T-cell differentiation declines toge ther with a change in the composition of T-cell subsets produced. Such an alteration of the thymic environment is responsible for the age-re lated change in peripheral T cells in number and in composition. Age c hange is observed in several intrinsic factors in the thymic environme nt which influence proliferation of thymocytes. These thymic intrinsic factors can either promote or inhibit proliferation of thymocytes, an d promoting factors generally decrease with age with a concomitant inc rease in inhibitory factors. Various endocrine hormones are important extrinsic factors influencing the thymic function. In fact, physiologi cal thymic involution can be intervened by manipulation of the endocri ne system, sometimes resulting in rejuvenation of immune functions to a certain extent. A specific strain of Buffalo rats has an unusual thy mus, which does not involute with age, and the functions of the T-cell dependent immune system do not decline with age. Such animals having hyperplastic thymus are relatively resistant to various kinds of stres s. Thus, restoration of immune functions in the aged animals appears t o be beneficial for them in coping with various diseases associated wi th age.