Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility
Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility
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DOI：
10.1073/pnas.1920795117
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发表时间：
2020-04-28
影响因子：
11.1
通讯作者：
Kondoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Kameda, Masahiro;Teruya, Takayuki;Kondoh, Hiroshi
随着人类社会的全球老龄化，与年龄相关的疾病变得越来越普遍。由于生理储备减少和与年龄相关的器官系统功能障碍增加，虚弱影响许多老年人，损害他们科普急性应激源的能力。虚弱的老年人通常表现出复杂的临床症状，包括认知功能障碍、低活动性和日常活动受损，其代谢基础仍然知之甚少。我们对19名虚弱和非虚弱老年患者的血液进行了非靶向的、全面的LC-MS代谢组学分析，这些患者使用埃德蒙顿虚弱量表、MoCA-J认知量表和TUG活动性量表进行临床评估。在检测的131种代谢物中，我们确定了22种用于虚弱、认知和低活动性的标记物，其中大多数在血液中丰富。虚弱标志物包括6个与认知特异性相关的标志物中的5个和12个与低活动性相关的标志物中的6个。这些重叠的标记物包括与抗氧化、肌肉或氮代谢以及氨基酸相关的代谢物，其中大多数在体弱的老年人中减少。五种与虚弱相关的代谢物减少了--1，5-脱水葡萄糖醇，乙酰肌肽，眼酸，亮氨酸和异亮氨酸--以前曾被报道为衰老的标志物，提供了人类衰老和虚弱之间的代谢联系。我们的研究结果清楚地表明，代谢物谱有效地区分脆弱和非脆弱。重要的是，抗氧化剂麦角硫因在虚弱时减少，具有神经保护作用。抗氧化剂水平下降导致的氧化应激可能是虚弱发病机制的关键脆弱性，加剧了与人类衰老相关的疾病。
As human society ages globally, age-related disorders are becoming increasingly common. Due to decreasing physiological reserves and increasing organ system dysfunction associated with age, frailty affects many elderly people, compromising their ability to cope with acute stressors. Frail elderly people commonly manifest complex clinical symptoms, including cognitive dysfunction, hypomobility, and impaired daily activity, the metabolic basis of which remains poorly understood. We applied untargeted, comprehensive LC-MS metabolomic analysis to human blood from 19 frail and nonfrail elderly patients who were clinically evaluated using the Edmonton Frail Scale, the MoCA-J for cognition, and the TUG for mobility. Among 131 metabolites assayed, we identified 22 markers for frailty, cognition, and hypomobility, most of which were abundant in blood. Frailty markers included 5 of 6 markers specifically related to cognition and 6 of 12 markers associated with hypomobility. These overlapping sets of markers included metabolites related to antioxidation, muscle or nitrogen metabolism, and amino acids, most of which are decreased in frail elderly people. Five frailty-related metabolites that decreased-1,5-anhydroglucitol, acetyl-carnosine, ophthalmic acid, leucine, and isoleucine-have been previously reported as markers of aging, providing a metabolic link between human aging and frailty. Our findings clearly indicate that metabolite profiles efficiently distinguish frailty from nonfrailty. Importantly, the antioxidant ergothioneine, which decreases in frailty, is neuroprotective. Oxidative stress resulting from diminished antioxidant levels could be a key vulnerability for the pathogenesis of frailty, exacerbating illnesses related to human aging.