TY - JOUR
T1 - Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity
AU - Hayashi, Taiki
AU - Zhang, Zhen
AU - Al-Eyd, Ghaith
AU - Sasaki, Atsushi
AU - Yasuda, Masanori
AU - Oyama, Masafumi
AU - Gomez-Sanchez, Celso E.
AU - Asakura, Hirotaka
AU - Seki, Tsugio
AU - Mukai, Kuniaki
AU - Nishimoto, Koshiro
N1 - Funding Information:
We thank Mr. Kouichi Kamada for his excellent technical help in this study and the China Scholarship Council government for the Scholarship to ZZ (#201,708,785,007). The authors acknowledge funding support from JSPS KAKENHI Grants (to KN [no. 15K10650 and 18K09205 ] and KM [no. 17K09890 ]); the Yamaguchi Endocrine Research Foundation (to KN) ; the Okinaka Memorial Foundation (to KN) . GS was supported by grants from the National Heart, Lung and Blood Institute R01 HL27255 and the National Institute of General Medical Sciences U54 GM115428 (CEGS) .
Publisher Copyright:
© 2019
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Adrenal gland
KW - Aldosterone synthase (CYP11B2)
KW - Aldosterone-producing adenoma (APA)
KW - Aldosterone-producing cell cluster (APCC)
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U2 - 10.1016/j.jsbmb.2019.04.010
DO - 10.1016/j.jsbmb.2019.04.010
M3 - Article
C2 - 30974191
AN - SCOPUS:85065227653
SN - 0960-0760
VL - 191
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
M1 - 105361
ER -
