Thymic re-growth and reactivation of thymic functions may be achieved in old animals by different endocrinological or nutritional manipulations such as, (a) treatment with melatonin, (b) implantation of a growth hormone (GH) secreting tumour cell line (GH3 cells) or treatment with exogeneous GH, (c) castration or treatment with exogenous luteinizing hormone-releasing hormone [LHRH], (d) treatment with exogenous thyroxin or triiodothyronine, and (e) nutritional interventions such as arginine or zinc supplementation. These data strongly suggest that thymic involution is a phenomenon secondary to age-related alterations in neuroendocrine-thymus interactions and that it is the disruption of these interactions in old age that is responsible for age-associated immune-neuroendocrine dysfunctions. The mechanisms involved in hormone-induced thymic reconstitution may be direct or indirect involving hormone receptors, cytokines and a trace element such as zinc, which is pivotal for the efficiency of neuroendocrine-immune network during the life-span of an organism. The effect of GH, thyroid hormones, and LHRH are due to specific hormone receptors on thymocytes and on thymic epithelial cells (TECs), which synthesize thymic peptides. Melatonin may also act through specific receptors on T-cells. In this context, the role of zinc, whose turnover is reduced in old age, is fundamental because of its involvement in zinc finger proteins that regulate gene expression for hormone receptors. However, the effects of zinc are multifaceted: it spans from the reactivation of zinc-dependent enzymes, to cell proliferation and apoptosis, to cytokines expression and to the reactivation of thymulin, which is a zinc-dependent thymic hormone required for intrathymic T-cell differentiation and maturation as well as for the homing of stem cells into the thymus. Therefore, the role of zinc is crucial in neuroendocrine-thymus interactions. According to current experimental data in animals and humans, the endocrinological manipulations for the maintenance of thymus function [e.g. by GH, thyroid hormones or melatonin] act via the zinc pool in restoring thymic activity and improving adaptive immunocompetence in ageing.
ASJC Scopus subject areas
- Clinical Neurology