Duke-National University of Singapore Medical School, Center for Aging, Research and Education Singapore.
Duke-National University of Singapore Medical School, Cardiovascular and Metabolic Disorders Programme, Singapore.
Mech Ageing Dev. 2021 Jan;193:111405. doi: 10.1016/j.mad.2020.111405. Epub 2020 Nov 17.
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.
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.
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.
We showed novel biomarkers for declining HGS, furthering molecular understanding and informing nutritional pre-emptive programs.
手握力（HGS）已被提出作为衰弱和肌少症的有力预测指标。因此，确定伴随衰老而下降的 HGS 的生物标志物可以加深我们对生物学基础的理解，为预防性干预提供信息。酰基辅酶 A（ACs）是线粒体脂肪酸代谢产生的代谢物，在影响肌肉的多种疾病中失调。然而，它们尚未被全面分析和研究其在预测 HGS 下降的变异性方面的效用，特别是在纵向研究中。因此，我们旨在：1）验证先前关于 ACs 与 HGS 之间无显著横断面关联的发现，2）检查基线 ACs 是否与社区居住的老年人 18 个月内 HGS 的下降和变异性均相关。
我们纳入了具有纵向测力计 HGS 测量值的参与者（N=121）。我们通过靶向血浆代谢组学分析来定量 ACs。然后进行多变量线性回归分析。
在横断面上，ACs 与 HGS 无显著相关性。在纵向研究中，基线短链二羧酸和羟基酰基辅酶 A（AC-DC/-OH）水平与 HGS 18 个月下降的变异性呈负相关，且具有显著的解释作用。特定的 AC 物种，C4-OH，解释了大部分可解释的方差。
我们展示了下降的 HGS 的新型生物标志物，进一步深入了解了分子机制，并为营养性预防性计划提供了信息。
