REVERSIBILITY OF THE THYMIC INVOLUTION AND OF AGE-RELATED PERIPHERAL IMMUNE DYSFUNCTIONS BY ZINC SUPPLEMENTATION IN OLD MICE

With advanced ageing the zinc pool undergoes progressive reduction as shown by the low zinc plasma levels and the negative crude zinc balanc e, both in humans and in rodents. It has been suggested that such zinc deficiency might be involved in many age-related immunological dysfun ctions, including thymic failure. The relevance of zinc for good funct ioning of the entire immune system is, at present, well documented. In particular, zinc is required to confer biological activity to one of the best-known thymic peptides, thymulin, which is responsible for cel l-mediated immunity. In deep zinc deficiencies, in humans and other an imals, the low thymulin levels are due not to a primary failure of the thymus, but to a reduced peripheral saturation of thymic hormones by zinc ions. In aged mice both a reduced peripheral saturation of the ho rmone and a decreased production by the thymus were present. Oral zinc supplementation in old mice (22 months old) for 1 month induced a com plete recovery of crude zinc balance from negative (-1.82) to positive values (+1.47), similar to those of young animals (+1.67). A full rec overy of thymic functions with a regrowth of the organ and a partial r estoration of the peripheral immune efficiency, as measured by mitogen responsiveness (PKA and ConA) and natural killer cell (NK) activity, were observed after zinc supplementation. These findings clearly pin-p oint the relevance of zinc for immune efficiency and suggest that the age-related thymic involution and peripheral immunological dysfunction s are not intrinsic and irreversible events but are largely dependent on the altered zinc pool.