Yuan Yin, Huang Xiaoming, Lin Siyang, Lin Wenwen, Huang Feng, Zhu Pengli
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, China.
Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
J Gerontol A Biol Sci Med Sci. 2025 Sep 19;80(10). doi: 10.1093/gerona/glaf127.
Subtle biological changes related to frailty may be undetected by standard clinical methods, and reliable biomarkers for frailty are still under investigation. This study was conducted to profile plasma metabolite patterns associated with frailty and validate the most significant metabolite for identifying and predicting frailty in cross-sectional and longitudinal analyses.
The "Fujian Prospective Aging Cohort" (ChiCTR 2000032949) enrolled 2,265 community-dwelling individuals aged 60 and above in 2020. Plasma metabolites were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Frailty was assessed using Fried's phenotype and the Frailty Index.
Widely targeted metabolomic analysis identified 889 metabolites. GAA was identified as the top frailty-associated candidate by ROC analysis and validated in a large cross-sectional cohort (AUC = 0.670). This cohort (N = 1,972) confirmed that subjects with lower GAA levels had a higher prevalence of frailty (P < .001). Multinomial logistic regression showed that higher GAA levels were significantly associated with lower odds of prefrailty and frailty; the ORs were 0.46 (95% CI: 0.32-0.66), and 0.15 (95% CI: 0.07-0.33) in the highest quartile, both P < .001). Over a 3-year follow-up period, a group-based trajectory model identified three Frailty Index trajectories: low-elevated (59.6%), moderate-elevated (34.1%), and high-elevated (6.3%). Subjects in the highest GAA quartile had a 36% and 66% lower likelihood of following moderate-elevated and high-elevated Frailty Index trajectories (P = .016 and P = .022).
This study identifies GAA as a potential metabolic biomarker for frailty. Higher GAA levels are associated with lower frailty odds and provide predictive value for a lower likelihood of frailty progression.
与衰弱相关的细微生物学变化可能无法通过标准临床方法检测到，用于衰弱的可靠生物标志物仍在研究中。本研究旨在剖析与衰弱相关的血浆代谢物模式，并在横断面和纵向分析中验证用于识别和预测衰弱的最显著代谢物。
“福建前瞻性衰老队列”（ChiCTR 2000032949）于2020年纳入了2265名60岁及以上的社区居住个体。使用超高效液相色谱-串联质谱法（UPLC-MS/MS）分析血浆代谢物。使用Fried表型和衰弱指数评估衰弱情况。
广泛靶向代谢组学分析鉴定出889种代谢物。通过ROC分析，GAA被确定为与衰弱相关的首要候选物，并在一个大型横断面队列中得到验证（AUC = 0.670）。该队列（N = 1972）证实，GAA水平较低的受试者衰弱患病率较高（P < 0.001）。多项逻辑回归显示，较高的GAA水平与衰弱前期和衰弱几率较低显著相关；在最高四分位数中，比值比分别为0.46（95% CI：0.32 - 0.66）和0.15（95% CI：0.07 - 0.33），两者P < 0.001）。在3年的随访期内，基于组的轨迹模型确定了三种衰弱指数轨迹：低升高（59.6%）、中升高（34.1%）和高升高（6.3%）。GAA最高四分位数的受试者遵循中升高和高升高衰弱指数轨迹的可能性分别降低36%和66%（P = 0.016和P = 0.022）。
本研究确定GAA为衰弱的潜在代谢生物标志物。较高的GAA水平与较低的衰弱几率相关，并为较低的衰弱进展可能性提供预测价值。
