Thymic regrowth and reactivation of thymic endocrine activity may be achieved even in old animals by different endocrinological or nutritional manipulations such as, (a) intrathymic transplantation of pineal gland or treatment with melatonin, (b) implantation of a growth hormone (GH) secreting tumor cell line or treatment with exogenous GH, (c) castration or treatment with exogenous luteinizing hormone-releasing hormone (LH-RH), (d) treatment with exogenous thyroxine 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 such interactions in old age that is responsible for age- associated dysfunction. With regard to the mechanisms involved in hormone- induced thymic reconstitution, it is at present, difficult to draw any definitive conclusions. The effect of GH, thyroid hormones, and LH-RH may be due to the presence on thymic epithelial cells supposed to produce thymic peptides, of the specific hormone receptors. Melatonin or other pineal factors may also act through specific receptors, but experimental evidence is still lacking. The role of zinc, whose turnover is usually reduced in old age, is diverse. The effects range from the reactivation of zinc-dependent enzymes, required for both cell proliferation and apoptosis, to the reactivation of thymulin, a zinc-dependent thymic hormone. The role of zinc may even be more crucial. According to recent preliminary data obtained both in animal and human studies, it appears that the above reported endocrinological manipulations capable of restoring thymic activity in old age, may act also by normalizing the altered zinc pool.
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