Background Health-related quality of life (HRQoL) measures are predictors of adverse health outcomes in older adults. Studies have demonstrated cross-sectional associations between HRQoL measures and blood-based biochemical markers. Acylcarnitines (ACs) are a class of metabolites generated in the mitochondria and are predictive of multiple geriatric syndromes. Changes in ACs reflect alterations in central carbon metabolic pathways. However, the prospective relationship between plasma acylcarnitines and declining HRQoL has not been examined. This study aimed to investigate both cross-sectional and longitudinal associations of baseline ACs with baseline and declining EuroQol-5 Dimension/ EuroQol Visual Analogue Scale (EQ-5D/ EQ-VAS) in community-dwelling older adults. Methods 120 community-dwelling older adults with EQ-5D/ EQ-VAS measurements at baseline and follow-up were included. We quantified ACs at baseline using targeted plasma metabolomics profiling. Multivariate regressions were performed to examine cross-sectional and longitudinal associations between the measures. Results Cross-sectionally, ACs showed no significant associations with either EQ-5D index or EQ-VAS scores. Longitudinally, multiple baseline short-chain ACs were significantly and inversely associated with declining EQ-5D index score, explaining up to 8.5% of variance in the decline. Conclusions Within a cohort of community-dwelling older adults who had high HRQoL at baseline, we showed that short-chain acylcarnitines are independent predictors of declining HRQoL. These findings reveal a novel association between central carbon metabolic pathways and declining HRQoL. Notably, dysregulation in mitochondrial central carbon metabolism could be detected prior to clinically important decline in HRQoL, providing the first evidence of objective biomarkers as novel predictors to monitor HRQoL in non-pharmacological interventions and epidemiology.

中文翻译：

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血浆酰基肉碱作为社区老年人健康相关生活质量下降的代谢特征：一项横断面和纵向相结合的试点研究


背景 健康相关生活质量 (HRQoL) 指标是老年人不良健康结果的预测因素。研究表明 HRQoL 测量值与血液生化标志物之间存在横向关联。酰基肉碱 (AC) 是线粒体中产生的一类代谢物，可预测多种老年综合征。 AC 的变化反映了中心碳代谢途径的变化。然而，血浆酰基肉碱与 HRQoL 下降之间的前瞻性关系尚未得到研究。本研究旨在调查社区老年人中基线 AC 与基线和下降的 EuroQol-5 维度/ EuroQol 视觉模拟量表 (EQ-5D/EQ-VAS) 的横断面和纵向关联。方法 纳入了 120 名社区老年人，他们在基线和随访时进行了 EQ-5D/EQ-VAS 测量。我们使用靶向血浆代谢组学分析在基线上量化 AC。进行多变量回归以检查测量之间的横截面和纵向关联。结果 从横截面来看，AC 与 EQ-5D 指数或 EQ-VAS 评分没有显着相关性。纵向来看，多个基线短链 AC 与 EQ-5D 指数得分下降呈显着负相关，解释了高达 8.5% 的下降方差。结论 在基线时 HRQoL 较高的社区老年人队列中，我们发现短链酰基肉碱是 HRQoL 下降的独立预测因素。这些发现揭示了中心碳代谢途径与 HRQoL 下降之间的新关联。 值得注意的是，线粒体中心碳代谢的失调可以在临床上重要的 HRQoL 下降之前被检测到，这为客观生物标志物作为非药物干预和流行病学中监测 HRQoL 的新预测因子提供了第一个证据。