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

The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system.
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DOI:
10.1016/j.neurobiolaging.2018.01.008
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发表时间:
2018-05
影响因子:
4.2
通讯作者:
Murphy D
Murphy D
中科院分区:
医学2区
文献类型:
--
作者:
Greenwood MP;Greenwood M;Romanova EV;Mecawi AS;Paterson A;Sarenac O;Japundžić-Žigon N;Antunes-Rodrigues J;Paton JFR;Sweedler JV;Murphy D

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老年人应对脱水等渗透性挑战的能力下降。我们对成年(3个月)和老年(18个月)大鼠下丘脑视上核(SON)的精氨酸抗利尿激素(AVP)生物合成过程和垂体后叶分泌活性进行了详细的分子分析,以全面分析AVP系统的年龄相关变化。通过基质辅助激光解吸/电离飞行时间质谱分析,我们鉴定了成年和老年大鼠在基础和脱水状态下垂体肽(包括AVP)的差异。在SON中,Avp基因转录增加,与衰老大鼠Avp启动子甲基化减少相一致。基于转录组数据,我们之前已经描述了一些新的脱水诱导的调节因子,这些因子参与了SON对渗透信号的反应。我们发现其中一些基因的表达随着年龄的增长而增加,而脱水诱导的SON中这些基因的表达在老年大鼠中减弱。总之,我们发现衰老在基因组、转录组和肽水平上改变了大鼠AVP系统。然而,在基础状态或脱水状态下,这些改变并不影响AVP的循环水平。
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.
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