Kazutaka Nanba1, Anand Vaidya1, Gordon H Williams1, Isabel Zheng1, Tobias Else1, William E Rainey2. 1. 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.). 2. 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.). wer@med.umich.edu.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: In adrenal tissue, the total CYP11B2-expressing area was negatively correlated with age (r=-0.431, P<0.0001), whereas the total aldosterone-producing cell cluster area was positively correlated with age (r=0.390, P<0.0001). The integrated ratio of aldosterone-producing cell cluster to CYP11B2-expressing area was most strongly and positively correlated with age (r=0.587, P<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, P<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, P<0.0001). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: In adrenal tissue, the total CYP11B2-expressing area was negatively correlated with age (r=-0.431, P<0.0001), whereas the total aldosterone-producing cell cluster area was positively correlated with age (r=0.390, P<0.0001). The integrated ratio of aldosterone-producing cell cluster to CYP11B2-expressing area was most strongly and positively correlated with age (r=0.587, P<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, P<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, P<0.0001). CONCLUSIONS: 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.
Authors: T Dekkers; M ter Meer; J W M Lenders; A R M Hermus; L Schultze Kool; J F Langenhuijsen; K Nishimoto; T Ogishima; K Mukai; E A B Azizan; B Tops; J Deinum; B Küsters Journal: J Clin Endocrinol Metab Date: 2014-04-23 Impact factor: 5.958
Authors: Michiel N Kerstens; Anneke C Muller Kobold; Marcel Volmer; Jan Koerts; Wim J Sluiter; Robin P F Dullaart Journal: Clin Chem Date: 2011-08-24 Impact factor: 8.327
Authors: Anand Vaidya; Patricia C Underwood; Paul N Hopkins; Xavier Jeunemaitre; Claudio Ferri; Gordon H Williams; Gail K Adler Journal: Hypertension Date: 2013-02-11 Impact factor: 10.190
Authors: Finn Holler; Daniel A Heinrich; Christian Adolf; Benjamin Lechner; Martin Bidlingmaier; Graeme Eisenhofer; Tracy Ann Williams; Martin Reincke Journal: Curr Hypertens Rep Date: 2019-09-03 Impact factor: 5.369