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Novel Metabolomics Markers Are Associated with Pre-Clinical Decline in Hand Grip Strength in Community-dwelling Older Adults
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2020-11-17 , DOI: 10.1016/j.mad.2020.111405
Ted Kheng Siang Ng 1 , Jean-Paul Kovalik 2 , Jianhong Ching 2 , Angelique W Chan 3 , David Bruce Matchar 4
Affiliation  

Background

Hand grip strength (HGS) has been proposed as a robust predictor for frailty and sarcopenia. Hence, identifying biomarkers for declining HGS accompanying aging could deepen our understanding of the biological underpinnings, informing pre-emptive intervention. Acylcarnitines (ACs) are metabolites generated by fatty acid metabolism in the mitochondria and are dysregulated in multiple disorders affecting the musculature. However, they have not been comprehensively profiled and examined regarding their utility in predicting variability in declining HGS, longitudinally. Thus, we aimed to: 1) validate previous findings on insignificant cross-sectional association between ACs and HGS, and 2) examine whether baseline ACs were associated with both decline and variability in HGS over 18 months, in community-dwelling older adults.

Methods

We included participants who had HGS measured with dynamometer longitudinally (N = 121). We quantified ACs by targeted plasma metabolomics profiling. Multivariable linear regressions were then performed.

Results

Cross-sectionally, ACs were not significantly associated with HGS. Longitudinally, baseline short-chain dicarboxylic and hydroxylated acylcarnitines (AC-DC/-OH) levels were inversely associated with and significantly explained the variability in 18-month decline in HGS. A specific AC species, the C4-OH, accounted for most of the variance explained.

Conclusions

We showed novel biomarkers for declining HGS, furthering molecular understanding and informing nutritional pre-emptive programs.



中文翻译:

新型代谢组学标志物与社区老年人临床前握力下降有关

背景

握力 (HGS) 已被提议作为虚弱和肌肉减少症的可靠预测指标。因此,识别伴随衰老而下降的 HGS 的生物标志物可以加深我们对生物学基础的理解,为先发制人的干预提供信息。酰基肉碱 (AC) 是由线粒体中的脂肪酸代谢产生的代谢物,在影响肌肉组织的多种疾病中失调。然而,尚未对它们在预测 HGS 下降的纵向变异性方面的效用进行全面的分析和检查。因此,我们的目标是:1)验证先前关于 AC 和 HGS 之间不显着的横断面关联的发现,以及 2)检查基线 AC 是否与社区居住的老年人 18 个月内 HGS 的下降和变异相关。

方法

我们纳入了使用测力计纵向测量 HGS 的参与者(N = 121)。我们通过靶向血浆代谢组学分析量化 AC。然后进行多变量线性回归。

结果

从横截面来看,AC 与 HGS 没有显着相关性。从纵向来看,基线短链二羧酸和羟基化酰基肉碱 (AC-DC/-OH) 水平与 HGS 18 个月下降的变异性呈负相关,并显着解释了这种变异性。一个特定的 AC 种类,C4-OH,占解释的大部分差异。

结论

我们展示了 HGS 下降的新生物标志物,进一步加深了分子理解,并为营养先发制人计划提供了信息。

更新日期:2020-11-17
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