Fabris N, Mocchegiani E, Provinciali M
Haematological Institute, S. Matteo Policlinic, University of Pavia, Italy.
Cell Mol Biol (Noisy-le-grand). 1997 Jun;43(4):529-41.
Thymic regrowth and reactivation of thymic endocrine activity may be achieved even in old animals by different endocrinological or nutritional manipulations. In particular: a) intrathymic transplant of pineal gland or treatment with melatonin; b) implantation of a growth hormone secreting tumor cell line or treatment with exogenous growth hormone; c) castration or treatment with exogenous LH-RH; d) treatment with exogenous thyroxine or triiodothyronine, and e) nutritional interventions such as arginine or zinc supplementation. These data strongly support the idea 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 which is responsible for most of age-associated dysfunctions. With regard to the mechanisms involved in hormone-induced thymic reconstitution, it is, at present, difficult to draw any definitive conclusion. 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 pineal derived factors may as well act through specific receptors but experimental demonstration is still lacking. The role of zinc, whose turnover is usually reduced in old age, is of quite wide-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 be even more crucial. According to recent preliminary data obtained both in animal and in man, 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.
即使是老龄动物，通过不同的内分泌或营养干预措施也可实现胸腺再生及胸腺内分泌活性的重新激活。具体如下：a）松果体胸腺内移植或褪黑素治疗；b）植入分泌生长激素的肿瘤细胞系或外源性生长激素治疗；c）去势或外源性促黄体生成素释放激素（LH-RH）治疗；d）外源性甲状腺素或三碘甲状腺原氨酸治疗；以及e）营养干预措施，如补充精氨酸或锌。这些数据有力地支持了这样一种观点，即胸腺退化是神经内分泌-胸腺相互作用中与年龄相关变化的继发现象，而正是老年时这种相互作用的破坏导致了大多数与年龄相关的功能障碍。关于激素诱导胸腺重建所涉及的机制，目前很难得出任何明确结论。生长激素、甲状腺激素和LH-RH的作用可能归因于假定能产生胸腺肽的胸腺上皮细胞上存在特定的激素受体。褪黑素或松果体衍生因子也可能通过特定受体起作用，但仍缺乏实验证据。锌的作用范围相当广泛，其周转在老年时通常会降低：从细胞增殖和凋亡所需的锌依赖性酶的重新激活，到锌依赖性胸腺激素胸腺素的重新激活。锌的作用可能更为关键。根据最近在动物和人类中获得的初步数据，上述能够恢复老年胸腺活性的内分泌操作，似乎也可能通过使改变的锌池正常化而起作用。
