title: Catecholamine Metabolism Induces Mitochondrial DNA Deletions and Leads to Severe Adrenal Degeneration during Aging.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Johannes Friedrich Georg
authors.initials: JF
authors.lastname: Neuhaus
authors.forename: Olivier Richard
authors.initials: OR
authors.lastname: Baris
authors.forename: Anne
authors.initials: A
authors.lastname: Kittelmann
authors.forename: Katrin
authors.initials: K
authors.lastname: Becker
authors.forename: Markus Alexander
authors.initials: MA
authors.lastname: Rothschild
authors.forename: Rudolf Josef
authors.initials: RJ
authors.lastname: Wiesner
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000648:ultrastructure*; D000375:Aging; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D002395:Catecholamines; D004272:DNA, Mitochondrial; D012333:RNA, Messenger