Ng Ted Kheng Siang, Wee Hai Ning, Ching Jianhong, Kovalik Jean-Paul, Chan Angelique W, Matchar David Bruce
Edson College of Nursing and Health Innovation, Arizona State University, USA.
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore.
J Gerontol A Biol Sci Med Sci. 2024 Mar 1;79(3). doi: 10.1093/gerona/glac114.
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 ACs 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.
One hundred and twenty 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.
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.
Within a cohort of community-dwelling older adults who had high HRQoL at baseline, we showed that higher levels of short-chain ACs are longitudinally associated with 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 nonpharmacological interventions and epidemiology.
健康相关生活质量（HRQoL）指标是老年人不良健康结局的预测因素。研究已证实HRQoL指标与血液生化标志物之间存在横断面关联。酰基肉碱（ACs）是一类在线粒体中产生的代谢物，可预测多种老年综合征。ACs的变化反映了中心碳代谢途径的改变。然而，血浆ACs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居住的老年人中，基线ACs与基线及下降的欧洲五维健康量表/欧洲视觉模拟量表（EQ-5D/EQ-VAS）之间的横断面和纵向关联。
纳入120名在基线和随访时进行了EQ-5D/EQ-VAS测量的社区居住老年人。我们使用靶向血浆代谢组学分析在基线时对ACs进行定量。进行多变量回归以检查各项指标之间的横断面和纵向关联。
横断面分析中，ACs与EQ-5D指数或EQ-VAS评分均无显著关联。纵向分析中，多个基线短链ACs与EQ-5D指数得分下降显著负相关，可解释下降方差的8.5%。
在一组基线时HRQoL较高的社区居住老年人中，我们发现较高水平的短链ACs与HRQoL下降存在纵向关联。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，在HRQoL出现临床重要下降之前，就可以检测到线粒体中心碳代谢的失调，这为在非药物干预和流行病学中监测HRQoL的新型预测指标提供了首个客观生物标志物的证据。
