Universität zu Köln

Neuhaus, Johannes Friedrich Georg, Baris, Olivier Richard, Kittelmann, Anne, Becker, Katrin, Rothschild, Markus Alexander and Wiesner, Rudolf Josef (2017). Catecholamine Metabolism Induces Mitochondrial DNA Deletions and Leads to Severe Adrenal Degeneration during Aging. Neuroendocrinology, 104 (1). S. 72 - 85. BASEL: KARGER. ISSN 1423-0194

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Abstract

Background: Aging is a multifactorial process characterized by organ loss of function and degeneration, but the mechanisms involved remain elusive. We have shown recently that catecholamine metabolism drives the accumulation of mitochondrial DNA (mtDNA) deletions in dopaminergic cells, which likely contribute to their degeneration during aging. Here we investigated whether the well-documented degeneration and altered function of adrenals during aging is linked to catecholamine production in the medulla followed by accumulation of mtDNA deletions. Material and Methods: We analyzed adrenal medullary and cortical samples of both murine and human origin covering a wide range of ages for mtDNA deletion content, mtDNA copy number, mitochondrial and cellular integrity as well as aging-related tissue changes such as fibrosis. Results: Indeed, we demonstrate in mice and humans that the adrenal medulla accumulates a strikingly high amount of mtDNA deletions with age, causing mitochondrial dysfunction in the adrenal medulla, but also in the cortex, accompanied by apoptosis and, more importantly, by severe inflammation and remarkable fibrosis. Additionally, a concomitant and dramatic loss of medullary and cortical cells is observed in old animals. Conclusion: Our results show that accumulation of mtDNA deletions, and the ensuing mitochondrial dysfunction, is a hallmark of adrenal aging, further strengthening the hypothesis that catecholamine metabolism is detrimental to mtDNA integrity, mitochondrial function and cell survival. Moreover, the cell loss potentially induced by mitochondrial dysfunction could explain the decline in adrenal hormonal and steroidal secretion during aging. (C) 2016 S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neuhaus, Johannes Friedrich Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Baris, Olivier Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Kittelmann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothschild, Markus Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf Josef UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-248580
DOI:	10.1159/000444680
Journal or Publication Title:	Neuroendocrinology
Volume:	104
Number:	1
Page Range:	S. 72 - 85
Date:	2017
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1423-0194
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SUBSTANTIA-NIGRA NEURONS; MONOAMINE-OXIDASE; HUMAN-HEART; SYMPATHOADRENAL SYSTEM; PHEOCHROMOCYTOMA CELLS; CLONAL EXPANSION; OXIDATIVE STRESS; AGE; DOPAMINE; RAT Multiple languages Endocrinology & Metabolism; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24858