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衰老的内分泌改变

Author
S Mitchell Harman, MD, PhD
Section Editors
Kenneth E Schmader, MD
Peter J Snyder, MD
Deputy Editor
Kathryn A Martin, MD
Translators
吴瑾, 副主任医师

引言

自19世纪以来，人们断断续续地尝试将衰老的变化归咎于一种或另一种内分泌缺陷，并努力通过各种内分泌治疗来逆转这些改变。直到今日，人们仍在寻找能永葆青春的激素，如广泛使用普拉睾酮(dehydroepiandrosterone, DHEA)作为“营养补充剂”。更有临床意义的是，超适应证地开具人生长激素(human growth hormone, hGH)和强效雄激素类固醇处方来对抗年龄相关的生长激素(growth hormone, GH)/胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)和睾酮(T)下降[分别称作“生长停止(somatopause)”和“男性更年期”]的情况日益增多。年龄相关的内分泌功能改变证据及其临床后果总结在此；疾病相关的改变见其他专题。 (参见“较年长男性睾酮缺乏的概述”和“Dehydroepiandrosterone and its sulfate”和“Growth hormone deficiency in adults”)

衰老的生理学

衰老的过程十分复杂，不能过分简单的将衰老等同于激素缺乏。生物衰老的特点是循序渐进的，在相当大的程度上，可以预测会有相应的细胞和组织功能的丧失，以致机体逐渐不太适合生殖和生存。这个过程的速度具有种属特异性，并且多个器官和系统之间表现出差异。在不同系统和个体之间，功能的退化是不同的，通常首先可检测到的是应激情况下的储备能力和恢复稳态的能力丧失，而后在静息状态时功能改变。

衰老潜在的基本机制尚不清楚。现有的最佳证据显示，衰老与损害核苷酸、蛋白质及脂膜功能的多种(未修复的)生化改变的积聚有关。这些变化可能包括自由基氧化[1]，但也有无酶糖基化[2]，以及表观遗传学改变，如DNA甲基化和组蛋白乙酰化[3]。分化细胞在多大程度上受衰老的影响决定了生理功能，而储备细胞(干细胞和前体细胞)受影响的程度决定了替代受损伤分化细胞和修复组织的能力[4]。部分研究表明，衰老有机体中存在循环因子，这些因子能抑制干细胞动员并妨碍损伤修复[4,5]。然而，所参与的细胞因子的生化特性仍有待明确。

一个描述得很充分的衰老现象是广泛分布的信号传导效能的退化。例如血管内皮对雌激素的血管舒张反应下降，可能与雌激素受体基因逐渐甲基化有关(一种表观遗传学改变)[6]，以及间质细胞对促性腺激素刺激的反应性下降(可能是由于细胞膜生物化学的改变)[7,8]。

内分泌改变 — 在考虑年长者内分泌功能变化时，鉴于该人群中症状性和无症状性疾病的患病率都很高，所以重要的是要区分衰老本身对内分泌生理的影响与年龄相关疾病引起的改变。这一区分在概念上很简单但在实践中却较困难。

                          

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