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人类血浆中生理衰老减速的代谢组学特征。

A metabolomic signature of decelerated physiological aging in human plasma.

机构信息

Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.

Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands.

出版信息

Geroscience. 2023 Dec;45(6):3147-3164. doi: 10.1007/s11357-023-00827-0. Epub 2023 May 31.

Abstract

The degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy longevity are gaining interest, both academically and in the public. While nutritional and physical interventions exist, efficacy is often difficult to determine. It is therefore imperative that an aging score measuring the biological aging process is available to the wider public. However, simple, interpret, and accessible biological aging scores are lacking. Here, we developed PhysiAge, a physiological aging score based on five accessible parameters that have influence on or reflect the aging process: (1) average daily step count, (2) blood glucose, (3) systolic blood pressure, (4) sex, and (5) age. Here, we found that compared to calendar age alone, PhysiAge better predicts mortality, as well as established muscle aging markers such as decrease in NAD levels, increase in oxidative stress, and decline in physical functioning. In order to demonstrate the usefulness of PhysiAge in identifying relevant factors associated with decelerated aging, we calculated PhysiAges for a cohort of aged individuals and obtained mass spectrometry-based blood plasma metabolomic profiles for each individual. Here, we identified a metabolic signature of decelerated aging, which included components of the TCA cycle, including malate, citrate, and isocitrate. Higher abundance of these metabolites was associated with decelerated aging, in line with supplementation studies in model organisms. PhysiAge represents an accessible way for people to track and intervene in their aging trajectories, and identifies a metabolic signature of decelerated aging in human blood plasma, which can be further studied for its causal involvement in human aging.

摘要

衰老过程中发生的退行性变化会增加患病和健康受损的风险。与此同时,针对衰老进行干预以促进健康长寿的方法在学术界和公众中越来越受到关注。虽然存在营养和身体干预措施,但疗效往往难以确定。因此,迫切需要有一种衡量生物衰老过程的衰老评分方法供更广泛的公众使用。然而,简单、易于解释和易于使用的生物衰老评分方法却缺乏。在这里,我们开发了 PhysiAge,这是一种基于五个可访问参数的生理衰老评分,这些参数对衰老过程有影响或反映了衰老过程:(1)平均日常步数,(2)血糖,(3)收缩压,(4)性别和(5)年龄。在这里,我们发现与仅使用日历年龄相比,PhysiAge 更好地预测了死亡率,以及 NAD 水平下降、氧化应激增加和身体功能下降等已建立的肌肉衰老标志物。为了证明 PhysiAge 在识别与延缓衰老相关的相关因素方面的有用性,我们为一组老年人计算了 PhysiAges,并为每个人获得了基于质谱的血液血浆代谢组学图谱。在这里,我们确定了一个延缓衰老的代谢特征,其中包括 TCA 循环的成分,如苹果酸、柠檬酸和异柠檬酸。这些代谢物丰度较高与衰老延缓有关,与模型生物的补充研究一致。PhysiAge 为人们跟踪和干预衰老轨迹提供了一种易于访问的方法,并在人类血液血浆中确定了延缓衰老的代谢特征,这可以进一步研究其在人类衰老中的因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5c0/10643795/1ee2a54941c4/11357_2023_827_Fig1_HTML.jpg

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