Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity
Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity
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DOI：
10.1016/j.jsbmb.2019.04.010
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发表时间：
2019-07-01
影响因子：
4.1
通讯作者：
Nishimoto, Koshiro
中科院分区：
文献类型：
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作者：
Hayashi, Taiki;Zhang, Zhen;Nishimoto, Koshiro
人类醛固酮合成酶(CYP11B2)的免疫组织化学研究表明，大多数醛固酮是在成人肾上腺被膜下的醛固酮生成细胞团(APCCs)中自主产生的，而不是生理性地在球状带(ZG)中产生的。APCCs有时被发现含有离子通道/泵基因的体细胞突变，并且APCCs的数量和大小随着年龄的增长而增加，直到50岁。在这项研究中，研究的目的是检查来自85名老年人的106个尸检肾上腺的APCC发育情况，这些老年人的年龄从50岁到103岁不等。我们获得了以下结果：(1)在更多的老年人ZG中，生理性的CYP11B2表达减弱；(2)APCCs的数量和大小随着年龄的增长而减少；(3)APCC在不同年龄段偶尔出现脱离；(4)偶发性微醛固酮腺瘤(APAs)和可能的APCC到APA过渡性病变(PAATL)主要在50-60岁的人中发现，而在更多的老年人中没有发现；pAATL是一个可能的名称，基于我们之前的研究结果，它由被膜下APCC样部分和内部APA样部分组成。因此，在50岁以上的个体中，肾上腺中表达CYP11B2的病变的形成以及ZG的增厚与死亡年龄呈负相关。考虑到本研究中使用的是尸检样本，无论是自主的还是生理的方式，不活跃地产生醛固酮可能对50岁以上的人具有生存优势。
Immunohistochemistry of human aldosterone synthase (CYP11B2) has revealed that most of aldosterone is autonomously produced in aldosterone-producing cell clusters (APCCs) beneath the capsule of adult adrenals rather than physiologically in the zona glomerulosa (ZG). APCCs have been occasionally found to harbor a somatic mutation of ion channel/pump genes, and number and size of APCCs increase with age until 50 years old. Herein, the objective of the study was to examine APCC development in 106 autopsied adrenals from 85 elderly individuals who died at ages from 50 to 103 years. We obtained the following results: (1) physiological CYP11B2 expression in ZG were attenuated in more elderly persons; (2) number and size of APCCs decreased with age; (3) detachment of APCC from the capsule appeared to occur occasionally over the wide range of the ages; and (4) incidental micro aldosterone-producing adenomas (APAs) and possible APCC-to-APA transitional lesions (pAATLs) were found primarily in samples from persons aged 50-60 years but not in samples from more elderly persons; pAATL was a putative designation based on our previous results indicating that it consisted of subcapsular APCC-like portion and inner APA-like portions. Thus, the formation of the CYP11B2-expressing lesions as well as thickening of the ZG in the adrenals were inversely correlated with age of death in the individuals aged over 50 years. Considering that autopsy samples were used in this study, inactive production of aldosterone regardless of autonomous or physiological manners may have survival advantages in individuals aged over 50 years.