Soendenbroe Casper, Heisterberg Mette F, Andersen Jesper L, Kjaer Michael, Mackey Abigail L
Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Cachexia Sarcopenia Muscle. 2025 Jun;16(3):e13832. doi: 10.1002/jcsm.13832.
Sarcopenia represents a major clinical and societal challenge facing rapidly aging populations. Accessible and specific biomarkers represent valuable tools, both in diagnosis and assessing the efficacy of therapeutic interventions. C-terminal agrin fragment (CAF) is the most commonly used blood-based biomarker of neuromuscular junction degradation in aging, inactivity and disease, but large unexplained interindividual variation exists, limiting its diagnostic and prognostic value. Exercise and medication may explain some of this variation. The aim of this study was to investigate the influence of a single bout (1EX) or 48 bouts (48EX) of heavy resistance exercise (EX), with or without angiotensin II type I receptor blocker (losartan (LOS)) supplementation, on serum CAF levels in healthy older men.
Eighty-three healthy, normotensive older men were enrolled in one of two randomized placebo (PLA) controlled trials. 1EX: 25 participants (EX ± LOS), with a mean age of 70 ± 7 years, had blood drawn before and after (4.5 h, Days 1, 4 and 7) a single bout of unilateral heavy resistance exercise of the quadriceps muscles. 48EX: at baseline, and after 8 and 16 weeks of a progressive heavy resistance exercise program, 58 participants (LOS-EX, n = 20; LOS-SED, n = 20; PLA-EX, n = 18), with a mean age of 72 ± 5 years, had blood drawn, and specific force (strength per unit mass) was measured by dynamometer and magnetic resonance imaging of the quadriceps muscles. Serum CAF was measured by ELISA.
At baseline, CAF showed weak correlations with age and leg lean mass (both R = 0.07, p < 0.05). With 48EX, specific force increased in both EX groups (LOS-EX + PLA-EX) by 13%-14% at 8 weeks and 14%-17% at 16 weeks (p < 0.0001), with no change in LOS-SED (p > 0.05), confirming the efficacy of the 48EX program. Serum CAF increased in LOS-EX and LOS-SED by 4%-7% at 8 weeks and 7%-9% at 16 weeks (p < 0.005) respectively, with no change in PLA-EX (p > 0.05). 1EX reduced CAF by 8% 1 day postexercise (p < 0.05), with no correlation to circulating creatine kinase levels (p > 0.05), a marker of muscle damage.
Serum CAF was unaffected by 16 weeks of EX but increased by LOS supplementation. 1EX, performed with one leg, acutely lowered serum CAF, albeit with substantial interindividual variability. These findings collectively identify novel stimuli of serum CAF turnover-drug interaction and time from last exercise bout to blood sampling. These findings add value to CAF as a neuromuscular biomarker and highlight important experimental design aspects for future clinical studies.
肌肉减少症是快速老龄化人口面临的一项重大临床和社会挑战。可获取且具有特异性的生物标志物在诊断以及评估治疗干预效果方面都是有价值的工具。C 端集聚蛋白片段（CAF）是衰老、缺乏运动和疾病中神经肌肉接头退化最常用的基于血液的生物标志物，但存在大量无法解释的个体间差异，限制了其诊断和预后价值。运动和药物可能解释部分这种差异。本研究的目的是调查单次（1EX）或 48 次（48EX）大强度抗阻运动（EX），无论是否补充血管紧张素 II 1 型受体阻滞剂（氯沙坦（LOS）），对健康老年男性血清 CAF 水平的影响。
83 名健康、血压正常的老年男性参加了两项随机安慰剂（PLA）对照试验之一。1EX：25 名参与者（EX±LOS），平均年龄 70±7 岁，在进行单次股四头肌单侧大强度抗阻运动前及运动后（4.5 小时、第 1、4 和 7 天）采血。48EX：在基线时，以及在进行为期 8 周和 16 周的渐进性大强度抗阻运动计划后，58 名参与者（LOS-EX，n = 20；LOS-SED，n = 20；PLA-EX，n = 18），平均年龄 72±5 岁，采血，并通过测力计和股四头肌磁共振成像测量比肌力（单位质量的力量）。通过酶联免疫吸附测定法测量血清 CAF。
在基线时，CAF 与年龄和腿部瘦体重呈弱相关（两者 R = 0.07，p < 0.05）。进行 48EX 时，两个 EX 组（LOS-EX + PLA-EX）的比肌力在 8 周时增加了 13% - 14%，在 16 周时增加了 14% - 17%（p < 0.0001），而 LOS-SED 组无变化（p > 0.05），证实了 48EX 计划的有效性。血清 CAF 在 LOS-EX 组和 LOS-SED 组分别在 8 周时增加了 4% - 7%，在 16 周时增加了 7% - 9%（p < 0.005），PLA-EX 组无变化（p > 0.05）。1EX 使运动后 1 天的 CAF 降低了 8%（p < 0.05），与循环肌酸激酶水平无相关性（p > 0.05），肌酸激酶是肌肉损伤的标志物。
血清 CAF 不受 16 周运动的影响，但补充 LOS 会使其增加。单腿进行的 1EX 可使血清 CAF 急性降低，尽管个体间存在很大差异。这些发现共同确定了血清 CAF 周转的新刺激因素——药物相互作用以及从最后一次运动 bout 到采血的时间。这些发现增加了 CAF 作为神经肌肉生物标志物的价值，并突出了未来临床研究重要的实验设计方面。
