Nanba Kazutaka, Vaidya Anand, Williams Gordon H, Zheng Isabel, Else Tobias, Rainey William E
From Departments of Molecular and Integrative Physiology & Internal Medicine, University of Michigan, Ann Arbor (K.N., I.Z., W.E.R.); Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (A.V., G.H.W.); and Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor (T.E., W.E.R.).
Circulation. 2017 Jul 25;136(4):347-355. doi: 10.1161/CIRCULATIONAHA.117.028201. Epub 2017 May 31.
Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and physiology is not well understood.
The relationship between age and adrenal aldosterone synthase (CYP11B2) expression was evaluated in 127 normal adrenal glands from deceased kidney donors (age, 9 months to 68 years). Following immunohistochemistry, CYP11B2-expressing area and areas of abnormal foci of CYP11B2-expressing cells, called aldosterone-producing cell clusters, were analyzed. In a separate ancillary clinical study of 677 participants without primary aldosteronism, who were studied on both high and restricted sodium diets (age, 18-71 years), we used multivariable linear regression to assess the independent associations between age and renin-angiotensin-aldosterone system physiology.
In adrenal tissue, the total CYP11B2-expressing area was negatively correlated with age (=-0.431, <0.0001), whereas the total aldosterone-producing cell cluster area was positively correlated with age (=0.390, <0.0001). The integrated ratio of aldosterone-producing cell cluster to CYP11B2-expressing area was most strongly and positively correlated with age (=0.587, <0.0001). When participants in the clinical study were maintained on a high sodium balance, renin activity progressively declined with older age, whereas serum and urinary aldosterone did not significantly decline. Correspondingly, the aldosterone-to-renin ratio was positively and independently associated with older age (adjusted β=+5.54 ng/dL per ng/mL per hour per 10 years, <0.001). In contrast, when participants were assessed under sodium-restricted conditions, physiological stimulation of aldosterone was blunted with older age (β=-4.6 ng/dL per 10 years, <0.0001).
Aging is associated with a pattern of decreased normal zona glomerulosa CYP11B2 expression and increased aldosterone-producing cell cluster expression. This histopathologic finding parallels an age-related autonomous aldosteronism and abnormal aldosterone physiology that provides 1 potential explanation for age-related cardiovascular risk.
衰老和醛固酮分泌异常均会增加患心血管疾病的风险；然而，衰老对醛固酮分泌及生理功能的影响尚未完全明确。
在127例来自已故肾供体的正常肾上腺组织（年龄9个月至68岁）中，评估年龄与肾上腺醛固酮合酶（CYP11B2）表达之间的关系。免疫组织化学检测后，分析CYP11B2表达区域以及表达CYP11B2的细胞异常聚集区域（即醛固酮分泌细胞团）。在另一项针对677例无原发性醛固酮增多症参与者的辅助临床研究中，这些参与者接受了高钠饮食和限钠饮食研究（年龄18 - 71岁），我们使用多变量线性回归评估年龄与肾素 - 血管紧张素 - 醛固酮系统生理功能之间的独立关联。
在肾上腺组织中，CYP11B2表达总面积与年龄呈负相关（r = -0.431，P < 0.0001），而醛固酮分泌细胞团总面积与年龄呈正相关（r = 0.390，P < 0.0001）。醛固酮分泌细胞团与CYP11B2表达区域的综合比值与年龄呈最强的正相关（r = 0.587，P < 0.0001）。在临床研究中，当参与者保持高钠平衡时，肾素活性随年龄增长逐渐下降，而血清和尿醛固酮水平无显著下降。相应地，醛固酮与肾素比值与年龄呈正相关且具有独立性（校正β = +5.54 ng/dL per ng/mL per hour per 10年，P < 0.001）。相反，当在限钠条件下评估参与者时，随着年龄增长醛固酮的生理刺激作用减弱（β = -4.6 ng/dL per 10年，P < 0.0001）。
衰老与正常球状带CYP11B2表达降低及醛固酮分泌细胞团表达增加的模式相关。这一组织病理学发现与年龄相关的自主性醛固酮增多症及醛固酮生理异常相平行，为年龄相关的心血管风险提供了一种潜在解释。
