Department of Endocrinology, Diabetes, and Metabolism, University Hospital Essen, University Duisburg-Essen, Germany.
Department of Life Sciences and Chemistry, Jacobs University Bremen, Germany.
J Gerontol A Biol Sci Med Sci. 2019 Jul 12;74(8):1162-1169. doi: 10.1093/gerona/glz040.
Clinical manifestation of hyperthyroidism and hypothyroidism vary with age, with an attenuated, oligosymptomatic presentation of thyroid dysfunction (TD) in older patients. We asked, whether in rodents TD phenotypes are influenced by age and whether this involves changes in systemic and/or organ thyroid hormone (TH) signaling. Chronic hyper- or hypothyroidism was induced in male mice at different life stages (5, 12, and 20 months). TH excess resulted in pronounced age-specific body weight changes (increase in youngest and decrease in old mice), neither explained by changes in food intake (similar increase at all ages), nor by thermogenic gene expression in brown adipose tissue (BAT) or TH serum concentrations. Relative increase in body temperature and activity were more pronounced in old compared to young hyperthyroid mice. An attenuated hypothyroid state was found in old mice for locomotor activity and in heart and BAT on functional (less bradycardia) and gene expression level (heart and BAT). In contrast, decrease in body weight was pronounced in old hypothyroid mice. Thus, age has divergent impact on features of TD in mice, whereby effects on highly complex systems, such as energy homeostasis are not proportional to serum TH state, in contrast to organ-specific responses in heart and BAT.
甲状腺功能亢进症和甲状腺功能减退症的临床表现因年龄而异，老年患者的甲状腺功能障碍（TD）表现为症状减轻、症状单一。我们曾询问过，TD 表型是否会受到年龄的影响，以及这是否涉及全身和/或器官甲状腺激素（TH）信号的变化。我们在不同的生命阶段（5、12 和 20 个月）诱导雄性小鼠发生慢性甲状腺功能亢进或甲状腺功能减退。TH 过多导致明显的年龄特异性体重变化（最小的增加和最老的减少），这既不能用食物摄入的变化（所有年龄段的摄入量相似）来解释，也不能用棕色脂肪组织（BAT）或 TH 血清浓度中的生热基因表达来解释。与年轻的甲状腺功能亢进症小鼠相比，年老的甲状腺功能亢进症小鼠的体温和活动的相对增加更为明显。年老的甲状腺功能减退症小鼠的运动活动和心脏及 BAT 的功能（心动过缓较少）和基因表达水平（心脏和 BAT）呈衰减性低甲状腺状态。相比之下，年老的甲状腺功能减退症小鼠的体重下降更为明显。因此，年龄对小鼠 TD 的特征有不同的影响，而对能量平衡等高度复杂系统的影响与血清 TH 状态不成比例，与心脏和 BAT 等器官特异性反应形成对比。
