Sapolsky R, Armanini M, Packan D, Tombaugh G
Department of Biological Sciences, Stanford University, California.
Endocrinol Metab Clin North Am. 1987 Dec;16(4):965-80.
This article has considered two themes that have permeated the gerontologic literature--namely, that aging is a time of decreased efficiency in responding to stress and that chronic stress can accelerate aspects of aging. Given the restricted framework of considering adrenocortical function (as a component of the stress response) and glucocorticoid over-exposure (as a component of chronic stress), there is considerable evidence for both of these ideas. The capacity of glucocorticoids to damage the rat hippocampus slowly over the life span and the glucocorticoid hypersecretion that seems to ensue during aging as a result of such hippocampal damage support these long-standing ideas. It should be noted that these two components interact with each other--excessive glucocorticoid secretion damages the hippocampus, and hippocampal damage produces excessive glucocorticoid secretion. This dysregulatory cascade appears to be a normal part of aging in the rat. The role of glucocorticoids in triggering programmed aging and death, while quite dramatic, is probably a phylogenetically rare event; it remains to be seen if the dysregulatory cascade of glucocorticoid excess in the rat is of relevance to aging in other species. Numerous published studies suggest that this cascade is not an obligatory aspect of normal human aging; rather, it appears to be a significant factor in the explanation of some features of pathologies associated with human aging.
本文探讨了贯穿老年学文献的两个主题，即衰老意味着应对压力的效率下降，以及慢性压力会加速衰老进程。鉴于在考虑肾上腺皮质功能（作为应激反应的一个组成部分）和糖皮质激素过度暴露（作为慢性压力的一个组成部分）这一有限框架下，有大量证据支持这两个观点。糖皮质激素在大鼠整个生命周期中缓慢损害海马体的能力，以及由于这种海马体损伤似乎在衰老过程中随之出现的糖皮质激素分泌过多现象，都支持了这些长期以来的观点。应当指出，这两个组成部分相互作用——糖皮质激素分泌过多会损害海马体，而海马体损伤又会导致糖皮质激素分泌过多。这种调节失调的级联反应似乎是大鼠衰老过程中的一个正常部分。糖皮质激素在引发程序性衰老和死亡方面的作用虽然相当显著，但可能是一种在系统发育上较为罕见的现象；大鼠体内糖皮质激素过量的调节失调级联反应是否与其他物种的衰老有关，仍有待观察。众多已发表的研究表明，这种级联反应并非正常人类衰老的必然方面；相反，它似乎是解释与人类衰老相关的某些病理特征的一个重要因素。
