追踪血浆 C 端神经胶质细胞黏附分子片段作为 18 至 87 岁男性神经肌肉衰退的生物标志物。

Tracking the Plasma C-Terminal Agrin Fragment as a Biomarker of Neuromuscular Decline in 18- to 87-Year-Old Men.

机构信息

Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

Space Medicine Research Group, Sharjah Institute for Medical and Health Sciences, University of Sharjah, 27272, Sharjah, United Arab Emirates.

出版信息

Mol Diagn Ther. 2024 Sep;28(5):611-620. doi: 10.1007/s40291-024-00724-y. Epub 2024 Jul 3.

DOI:10.1007/s40291-024-00724-y

PMID:38961032

Abstract

OBJECTIVES

Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown.

METHODS

We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed.

RESULTS

We found an age-associated increase in CAF22 from young (100.9 ± 29 pmol) to middle-aged (128.3 ± 38.7 pmol) and older men (171.5 ± 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 ± 6.1 kg, 30.2 ± 5.2 kg, and 26.6 ± 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 ± 1.02 kg/m, 7.65 ± 0.92 kg/m, 6.87 ± 0.93 kg/m, for young, middle-aged, and old men, respectively), and gait speed (1.29 ± 0.24 m/s, 1.05 ± 0.16 m/s, and 0.81 ± 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men.

CONCLUSION

Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed.

摘要

目的

血浆 C 端神经递质结合蛋白片段 22（CAF22）是神经肌肉接头的一种降解产物，是肌肉减少的潜在生物标志物。然而，从青春期到 80 岁的 CAF22 水平尚不清楚。

方法

我们评估了年轻人（18-34 岁，n=203）、中年人（35-59 岁，n=163）和老年人（60-87 岁，n=143）的 CAF22、握力（HGS）、四肢骨骼肌质量指数（ASMI）和步态速度。

结果

我们发现 CAF22 从年轻人（100.9±29 pmol）到中年人（128.3±38.7 pmol）和老年人（171.5±35.5 pmol）呈年龄相关增加（均 p<0.05）。这伴随着 HGS（37.7±6.1 kg、30.2±5.2 kg 和 26.6±4.7 kg，分别为年轻人、中年人、老年人）、ASMI（8.02±1.02 kg/m、7.65±0.92 kg/m 和 6.87±0.93 kg/m，分别为年轻人、中年人、老年人）和步态速度（1.29±0.24 m/s、1.05±0.16 m/s 和 0.81±0.13 m/s，分别为年轻人、中年人、老年人）的逐渐降低。在调整年龄后，我们发现 CAF22 与 HGS（-0.0574，p<0.001）和步态速度（-0.0162，p<0.001）在累积队列中呈负相关。受试者工作特征分析显示，血浆 CAF22 在诊断肌肉无力（HGS<27 kg）（中年人；AUC=0.731，95%CI=0.629-0.831，p<0.001，老年人；AUC=0.816，95%CI=0.761-0.833，p<0.001）和低步态速度（0.8 m/s）（中年人；AUC=0.737，95%CI=0.602-0.871，p<0.001，老年人；AUC=0.829，95%CI=0.772-0.886，p<0.001）方面具有显著疗效，并且在诊断肌肉减少症（中年人；AUC=0.701，95%CI=0.536-0.865，p=0.032，老年人；AUC=0.822，95%CI=0.759-0.884，p<0.001）方面也具有中等疗效。