Metabolomic approaches to the normal aging process

Metabolomic approaches to the normal aging process
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DOI:
10.1007/s11306-014-0663-9
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发表时间:
2014-12-01
期刊:
影响因子:
3.6
通讯作者:
Jung, Byung Hwa
Jung, Byung Hwa
中科院分区:
医学3区
文献类型:
--
作者:
Lee, Soo Hyun;Park, Sungha;Jung, Byung Hwa

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衰老是一个多方面的过程,涉及随着时间的推移生物系统中各种有害变化的积累,因此在整个衰老过程中检测到细胞代谢的显著变化。在本研究中,相关的正常衰老过程的代谢过程进行了研究,通过非靶向代谢组学,使用液相色谱-质谱。为了排除生理和环境差异,分析了来自两个独立研究组的血浆中的代谢谱和相关代谢途径,这两个研究组包括两个不同年龄的健康个体队列,老年人和年轻人。第一组从城市医院招募,第二组从农村社区招募。脂肪酸β-氧化、甘油磷脂代谢和鞘脂代谢的改变被确定为与正常衰老相关的重要代谢途径。还发现鞘脂代谢中的鞘氨醇、β-氧化中的长链酰基肉毒碱和甘油磷脂代谢中的溶血磷脂酰胆碱(LysoPCs)可能是衰老过程中的关键候选代谢物。这些结果表明,最健康的个体的代谢谱可能与线粒体的正常功能有关,线粒体是氧化还原稳态的主要细胞器,如由其低酰基肉毒碱与L-肉毒碱的比率和血浆中低水平的LysoPC和鞘氨醇所指示的。目前的研究为整个衰老过程提供了重要的贡献。
Aging is a multifaceted process involving the accumulation of diverse deleterious changes in biological systems over time, so significant alterations in cellular metabolism are detected throughout aging. In the present study, the metabolic processes relevant to the normal aging process were investigated via non-targeted metabolomics using liquid chromatography-mass spectrometry. To exclude physiological and environmental differences, the metabolic profiles and the relevant metabolic pathways were analyzed in plasma from two separate study groups comprising two distinctly aged cohorts of healthy individuals, the elderly and the younger. The first group was recruited from an urban hospital, and the second group was recruited from a rural community. Alterations in fatty acid beta-oxidation, glycerophospholipid metabolism, and sphingolipid metabolism were identified as significant metabolic pathways relevant to normal aging. It was also found that sphingosine in sphingolipid metabolism, long-chain acylcarnitines in beta-oxidation, and lysophosphatidylcholines (LysoPCs) in glycerophospholipid metabolism could be critical candidate metabolites in the aging process. These results suggest that the metabolic profile of the healthiest individuals could be associated with the normal function of mitochondria, the primary organelle of redox homeostasis, as indicated by their low acylcarnitine to l-carnitine ratio and low levels of LysoPCs and sphingosine in plasma. The present study provides a critical contribution to the entire picture of the aging process.