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

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.

Transcription factor Creb3l1 regulates the synthesis of prohormone convertase enzyme PC1/3 in endocrine cells

“…We have previously reported up‐regulation of the Creb3l1 gene in the hypothalamus following dehydration, salt loading and hyperosmotic stress 12 and, in the present study, we demonstrate increased Pcsk1 expression under these same conditions. During dehydration, AVP biosynthesis increases, 40,41 and an additional demand for this peptide necessitates changes in cell components necessary for processing and secretion 42 . Because the AVP prohormone can be processed by PC1/3 in vitro 31 and in vivo, 43 and PC1/3 is highly expressed in AVP and oxytocin neurones of the hypothalamus, 18 it is not surprising that we see an increase in PC1/3 expression under conditions that stimulate the AVP system.…”

Utilizing an Animal Model to Identify Brain Neurodegeneration-Related Biomarkers in Aging

“…The function of proSAAS includes the inhibition of endogenous prohormone convertases 1, which has catalytic activities of releasing hormones or neuropeptides [ 47 ]. In addition, since proSAA Simmunal responses can be observed in the brains of patients with dementia syndromes (such as Alzheimer’s disease and Parkinson’s disease), this renders proSAAS as a potential therapeutic target in neurodegenerative diseases [ 48 , 49 , 50 ]. These may be markers for mild neurological disorders.…”

Heterogeneity and Dynamics of Vasculature in the Endocrine System During Aging and Disease

“…Adipose tissue has been shown to increase plasma ACTH levels and impair adrenal sensitivity to ACTH ( Ferdinand et al, 2012 ). In the neurohypophysis, arginine vasopressin (AVP) secretion increases with age ( Terwel et al, 1992 ; Greenwood et al, 2018 ). Systemically AVP triggers water reabsorption in the kidneys.…”