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

Michael P. Greenwood*, Mingkwan Greenwood, Elena V. Romanova, Andre S. Mecawi, Alex Paterson, Olivera Sarenac, Nina Japundžić-Žigon, José Antunes-Rodrigues, Julian F.R. Paton, Jonathan V. Sweedler, David Murphy

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

3 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)178-191
Number of pages14
JournalNeurobiology of Aging
Volume65
Early online date31 Jan 2018
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Aging
  • Gene expression
  • Methylation
  • Peptidomics
  • Supraoptic nucleus
  • Vasopressin

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    Greenwood, M. P., Greenwood, M., Romanova, E. V., Mecawi, A. S., Paterson, A., Sarenac, O., Japundžić-Žigon, N., Antunes-Rodrigues, J., Paton, J. F. R., Sweedler, J. V., & Murphy, D. (2018). The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system. Neurobiology of Aging, 65, 178-191. https://doi.org/10.1016/j.neurobiolaging.2018.01.008