Age-related changes in metabolites in young donor livers and old recipient sera after liver transplantation from young to old rats.
Age-related changes in metabolites in young donor livers and old recipient sera after liver transplantation from young to old rats.
复制标题
年轻大鼠肝移植至老年大鼠肝移植后年轻供体肝脏和老年受体血清中代谢物与年龄相关的变化
作者：
Han Q;Li H;Jia M;Wang L;Zhao Y;Zhang M;Zhang Q;Meng Z;Shao J;Yang Y;Zhu L
肝脏老化不仅损害肝功能，还损害全身新陈代谢。为了更好地了解肝脏老化的机制，我们将年轻大鼠的肝脏移植到年轻和老年大鼠身上，并进行了非靶向代谢组学研究，以检测肝脏组织和血清中代谢物的变化。未行肝移植的老年大鼠和青年大鼠肝脏中共检测到153种代谢物，血清中有83种代谢物存在差异，其中7种代谢物在肝脏和血清中均有不同的存在。肝移植后5周，青年供者肝脏中的25种代谢物水平与老年大鼠相似，这一结果可能是由于老年受体全身环境对青年肝脏的影响所致。改变的25种代谢物包括有机酸及其衍生物、脂质和类脂分子等。在血清中，78种代谢物在幼年和老年大鼠之间差异显著，而在老年受体大鼠中差异不显著，使老年受体与年轻受体的代谢谱更接近。最后，结合上述代谢数据和GEO的转录组数据，我们发现肝脏中的代谢产物和基因在9条代谢途径中得到了丰富，包括甘油磷脂、花生四烯酸、组氨酸和亚油酸。因此，这项研究揭示了重要的与年龄相关的代谢物和潜在的途径，以及肝脏和全身环境之间的相互作用。衰老与代谢紊乱有关。为了更好地了解潜在的机制，我们将年轻大鼠的肝脏移植到年轻和老年大鼠身上。对肝脏和血清中不同代谢物的分析表明，尽管年轻的供体肝脏在老年受者中经历了衰老，但它们可以通过循环使老年受者受益。整合的代谢组和转录组图谱提示在肝脏老化过程中代谢途径改变。
Liver ageing not only damages liver function but also harms systemic metabolism. To better understand the mechanisms underlying liver ageing, we transplanted the livers of young rats to young and old rats and performed untargeted metabolomics to detect changes in the metabolites in the liver tissues and sera. A total of 153 metabolites in the livers and 83 metabolites in the sera were different between the old and young rats that did not undergo liver transplantation; among these metabolites, 7 different metabolites were observed in both the livers and sera. Five weeks after liver transplantation, the levels of 25 metabolites in the young donor livers were similar to those in the old rats, and this result probably occurred due to the effect of the whole‐body environment of the older recipients on the young livers. The 25 altered metabolites included organic acids and derivatives, lipids and lipid‐like molecules, etc. In the sera, the differences in 78 metabolites, which were significant between the young and old rats, were insignificant in the old recipient rats and made the metabolic profile of the old recipients more similar to that of the young recipients. Finally, combining the above metabolomic data with the transcriptomic data from the GEO, we found that the altered metabolites and genes in the liver were enriched in 9 metabolic pathways, including glycerophospholipid, arachidonic acid, histidine and linoleate. Thus, this study revealed important age‐related metabolites and potential pathways as well as the interaction between the liver and the whole‐body environment. Aging is related to metabolic disorder. To better understand the underlying mechanisms, we transplanted livers of young rats to young and old rats. Analyses of differential metabolites in the livers and sera revealed that while the young donor livers underwent aging in the old recipients, they could benefit the old recipients through circulation. Integrated metabolomic and transcriptomic profiles suggested altered metabolic pathways during liver aging.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
2.6
作者：
Kroll, Jens
通讯作者：
Kroll, Jens
影响因子：
4.1
作者：
Pang, Zhiqiang;Chong, Jasmine;Xia, Jianguo
通讯作者：
Xia, Jianguo
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
DOI：
10.1126/science.aaw2622
发表时间：
2020-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Horowitz AM;Fan X;Bieri G;Smith LK;Sanchez-Diaz CI;Schroer AB;Gontier G;Casaletto KB;Kramer JH;Williams KE;Villeda SA
通讯作者：
Villeda SA