Age-associated elevation of hypothalamic, threshold to feedback control, and its role in development, ageine, and disease.
Age-associated elevation of hypothalamic, threshold to feedback control, and its role in development, ageine, and disease.
复制标题
与年龄相关的下丘脑升高、反馈控制阈值及其在发育、年龄和疾病中的作用。
DOI：
10.1016/s0140-6736(71)91721-1
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发表时间：
1971
期刊：
影响因子：
168.9
通讯作者：
V. Dilman
中科院分区：
文献类型：
--
作者：
V. Dilman
在这一假设中，我们认为发育和衰老的遗传程序的关键过程是下丘脑对反馈抑制的敏感性阈值的逐渐升高。这种下丘脑反馈为发育中的分化生物体提供了内环境的稳定性。下丘脑阈值的升高和由此引起的一些下丘脑中枢活动的增加，导致几个外周内分泌腺活动的代偿性增加。由于代偿过程，自我调节机制得以维持，尽管下丘脑对衰老引起的homœostatic抑制的抵抗力越来越强。然而，这些变化逐渐导致永久偏离了内部环境的恒定规律，最终产生了衰老的特定病变。这一假说允许解释为什么在代谢性肥胖、前驱糖尿病和成人糖尿病、动脉粥样硬化、更年期和某些形式的癌症等临床不同疾病中观察到与正常衰老有关的干扰。关于衰老的神经内分泌机制的提升性质的假设使我们能够找到影响衰老和年龄相关疾病机制的新手段。这些方法应该会增加下丘脑对生理反馈抑制的敏感性。
In this hypothesis it is suggested that the key process in the genetic programme of development and ageing is a gradual elevation of the threshold of sensitivity of the hypothalamus to feedback suppression. This hypothalamic feedback provides stability of the internal environment in the developing differentiated organism. The elevation of the hypothalamic threshold and the resulting increase of the activity of a number of hypothalamic centres lead to a compensatory increase in the activity of several peripheral endocrine glands. Owing to compensatory processes, the mechanism of self-regulation is maintained, despite the growing resistance of the hypothalamus to homœostatic suppression caused by ageing. However, these alterations gradually result in permanent deviations from the law of constancy of the internal environment, ultimately producing the specific lesions of ageing. This hypothesis permits an explanation of why the disturbances which are pertinent to normal ageing are observed in such clinically different diseases as metabolic obesity, prediabetes and adult diabetes, atherosclerosis, climacteric, and some forms of cancer. The hypothesis on the elevating nature of the neuroendocrine mechanism of ageing permits us to find new means for influencing the mechanism of ageing and age-related disease. These means should increase the sensitivity of hypothalamus to physiological feedback suppression.