TY - JOUR
T1 - The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system
AU - Greenwood, Michael P.
AU - Greenwood, Mingkwan
AU - Romanova, Elena V.
AU - Mecawi, Andre S.
AU - Paterson, Alex
AU - Sarenac, Olivera
AU - Japundžić-Žigon, Nina
AU - Antunes-Rodrigues, José
AU - Paton, Julian F.R.
AU - Sweedler, Jonathan V.
AU - Murphy, David
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Aging
KW - Gene expression
KW - Methylation
KW - Peptidomics
KW - Supraoptic nucleus
KW - Vasopressin
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U2 - 10.1016/j.neurobiolaging.2018.01.008
DO - 10.1016/j.neurobiolaging.2018.01.008
M3 - Article
C2 - 29494864
AN - SCOPUS:85042491332
SN - 0197-4580
VL - 65
SP - 178
EP - 191
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -