Circulating Metabolomic Analysis following Cecal Ligation and Puncture in Young and Aged Mice Reveals Age-Associated Temporal Shifts in Nicotinamide and Histidine/Histamine Metabolic Pathways.
Circulating Metabolomic Analysis following Cecal Ligation and Puncture in Young and Aged Mice Reveals Age-Associated Temporal Shifts in Nicotinamide and Histidine/Histamine Metabolic Pathways.
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DOI：
10.1155/2021/5534241
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发表时间：
2021
影响因子：
--
通讯作者：
Zuckerbraun B
中科院分区：
文献类型：
--
作者：
Cyr A;Kohut L;Chambers L;Stratimirovic S;Zuckerbraun B
与受到同样压力的年轻人相比，老年人在急性应激源后发病和死亡的风险更高。对与年龄相关的代谢变化的评估可以确定特定的治疗靶点，以改善老年人感染等急性应激源的结果。因此，我们比较了盲肠结扎穿刺（CLP）（一种公认的急性感染和应激模型）后年轻和年老小鼠的血浆代谢组。 在假手术（仅剖腹手术）或 CLP 之前，对年轻（9-17 周）和老年（78-96 周）雄性 C57bl/6 小鼠进行眼眶后放血并进行两周恢复。干预后4小时、8小时或12小时处死动物，从血液中分离血浆用于后续分析。对样品进行代谢组学分析（Metabolon；达勒姆，北卡罗来纳州）。 老年动物的术中死亡率高于年轻动物（30.2% vs. 17.4%，χ2p = 0.0004），证实了脆弱性增强。对 566 种代谢物的主成分分析和部分最小二乘判别分析表明，年轻和老年动物在假手术或 CLP 后发生了明显的代谢组变化。使用一致的统计方法鉴定感兴趣的代谢物表明，组氨酸/组胺途径和烟酰胺途径在 CLP 后都有显着的与年龄相关的改变。 非靶向血浆代谢组学的应用确定了年轻和老年动物对 CLP 代谢组学反应的关键途径。最终，这些数据为未来的机制研究提供了坚实的基础，可能有助于改善体弱患者应对感染、创伤或手术等急性应激源的结果。
Aged individuals are at higher risk for morbidity and mortality following acute stressors than similarly stressed young people. Evaluation of age-associated metabolic changes could lead to the identification of specific therapeutic targets to improve outcomes from acute stressors, such as infections, in the elderly. We thus compared the plasma metabolomes of both young and old mice following cecal ligation and puncture (CLP), an accepted model of acute infection and stress. Young (9-17 wks) and aged (78-96 wks) male C57bl/6 mice were subjected to a retro-orbital bleed and two-week recovery prior to sham surgery (laparotomy alone) or CLP. Animals were sacrificed at 4 h, 8 h, or 12 h following intervention, and plasma was isolated from blood for subsequent analysis. Metabolomic analysis of samples were performed (Metabolon; Durham, NC). Aged animals demonstrated greater intraprocedural mortality than young (30.2% vs. 17.4%, χ2p = 0.0004), confirming enhanced frailty. Principal component analysis and partial-least squares discriminant analysis of 566 metabolites demonstrated distinct metabolomic shifts following sham surgery or CLP in both young and aged animals. Identification of metabolites of interest using a consensus statistical approach revealed that both the histidine/histamine pathway and the nicotinamide pathway have significant age-associated alterations following CLP. The application of untargeted plasma metabolomics identified key pathways underpinning metabolomic responses to CLP in both young and aged animals. Ultimately, these data provide a robust foundation for future mechanistic studies that may assist in improving outcomes in frail patients in response to acute stressors such as infection, trauma, or surgery.
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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：
5
作者：
Fujii, T;Takaoka, M;Matsumura, Y
通讯作者：
Matsumura, Y
DOI：
10.1016/j.bbrc.2004.09.136
发表时间：
2004-11-12
影响因子：
3.1
作者：
Shao, L;Li, QH;Tan, Z
通讯作者：
Tan, Z
影响因子：
4.1
作者：
Pang, Zhiqiang;Chong, Jasmine;Xia, Jianguo
通讯作者：
Xia, Jianguo
影响因子：
38.9
作者：
Seymour, Christopher W.;Yende, Sachin;Scott, Melanie J.;Pribis, John;Mohney, Robert P.;Bell, Lauren N.;Chen, Yi-Fan;Zuckerbraun, Brian S.;Bigbee, William L.;Yealy, Donald M.;Weissfeld, Lisa;Kellum, John A.;Angus, Derek C.
通讯作者：
Angus, Derek C.