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The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system

Greenwood MP 1 , Greenwood M 2 , Romanova EV 3 , Mecawi AS 4 , Paterson A 2 , Sarenac O 5 Show all authors , Japundžić-Žigon N 6 , Antunes-Rodrigues J 7 , Paton JFR 8 , Sweedler JV 3 , Murphy D 9

Affiliations 

  • 1 School of Clinical Sciences, University of Bristol, Bristol, England. Electronic address: mike.greenwood@bristol.ac.uk
  • 2 School of Clinical Sciences, University of Bristol, Bristol, England
  • 3 Department of Chemistry and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA
  • 4 School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil; Department of Physiology, University of Malaya, Kuala Lumpur, Malaysia; Department of Physiological Sciences, Institute of Biological and Health Sciênces, Federal Rural University of Rio de Janeiro, Seropedica, Brazil
  • 5 School of Clinical Sciences, University of Bristol, Bristol, England; Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • 6 Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • 7 School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
  • 8 School of Physiology and Pharmacology, University of Bristol, Bristol, England
  • 9 School of Clinical Sciences, University of Bristol, Bristol, England; Department of Physiology, University of Malaya, Kuala Lumpur, Malaysia
Neurobiol Aging, 2018 05;65:178-191.
PMID: 29494864 DOI: 10.1016/j.neurobiolaging.2018.01.008

Abstract

Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased Avp gene transcription, coincided with reduced Avp promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels. These alterations however did not affect circulating levels of AVP in basal or dehydrated states.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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