Gupta Deepashree, Morley John E
Division of Endocrinology, Saint Louis University, Missouri, St. Louis; Divisions of Endocrinology and Geriatric Medicine, Saint Louis University, Missouri, St. Louis.
Compr Physiol. 2014 Oct;4(4):1495-510. doi: 10.1002/cphy.c130049.
Human aging is associated with increasing frailty and morbidity which can result in significant disability. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to aging-related diseases like depression, cognitive deficits, and Alzheimer's disease in some older individuals. In addition to neuro-cognitive dysfunction, it has also been associated with declining physical performance possibly due to sarcopenia. This article reviews the pathophysiology of HPA dysfunction with respect to increased basal adrenocorticotropic hormone (ACTH) and cortisol secretion, decreased glucocorticoid (GC) negative feedback at the level of the paraventricular nucleus (PVN) of the hypothalamus, hippocampus (HC), and prefrontal cortex (PFC), and flattening of diurnal pattern of cortisol release. It is possible that the increased cortisol secretion is secondary to peripheral conversion from cortisone. There is a decline in pregnolone secretion and C-19 steroids (DHEA) with aging. There is a small decrease in aldosterone with aging, but a subset of the older population have a genetic predisposition to develop hyperaldosteronism due to the increased ACTH stimulation. The understanding of the HPA axis and aging remains a complex area with conflicting studies leading to controversial interpretations.
人类衰老与身体虚弱和发病率增加相关，这可能导致严重残疾。下丘脑 - 垂体 - 肾上腺（HPA）轴功能障碍可能在一些老年人中导致与衰老相关的疾病，如抑郁症、认知缺陷和阿尔茨海默病。除了神经认知功能障碍外，它还可能与身体机能下降有关，这可能是由于肌肉减少症所致。本文综述了HPA功能障碍的病理生理学，包括基础促肾上腺皮质激素（ACTH）和皮质醇分泌增加、下丘脑室旁核（PVN）、海马体（HC）和前额叶皮质（PFC）水平的糖皮质激素（GC）负反馈降低以及皮质醇释放昼夜模式变平。皮质醇分泌增加可能继发于可的松的外周转化。随着年龄增长，孕烯醇酮分泌和C - 19类固醇（脱氢表雄酮，DHEA）减少。随着年龄增长，醛固酮略有下降，但一部分老年人群因ACTH刺激增加而有发生醛固酮增多症的遗传易感性。对HPA轴与衰老的理解仍然是一个复杂的领域，相互矛盾的研究导致了有争议的解释。
