NMR Metabolomic response to exercise in young and older human plasma

Background: The favorable health-promoting adaptations to exercise result
from cumulative responses to individual bouts of physical activity. Older
adults often exhibit anabolic resistance; a phenomenon whereby the
anabolic responses to exercise and nutrition are attenuated in skeletal
muscle. The mechanisms contributing to age-related anabolic resistance are
emerging, but our understanding of how chronological age influences
responsiveness to exercise is incomplete. The objective was to determine
the effects of healthy aging on peripheral blood metabolomic response to a
single bout of resistance exercise and whether any metabolites in
circulation are predictive of anabolic response in skeletal muscle.
Methods: Thirty young (20-35 years) and 49 older (65-85 years) men and
women were studied in a cross-sectional manner.  Participants
completed a single bout of resistance exercise consisting of eight sets of
10 repetitions of unilateral knee extension at 70% of one-repetition
maximum. Blood samples were collected before exercise, immediately post
exercise, and 30-, 90-, and 180-minutes into recovery. Proton nuclear
magnetic resonance spectroscopy was used to profile circulating
metabolites at all timepoints. Serial muscle biopsies were collected for
measuring muscle protein synthesis rates.  Results: Our
analysis revealed that one bout of resistance exercise elicits significant
changes in 26 of 33 measured plasma metabolites, reflecting alterations in
several biological processes. Furthermore, 12 metabolites demonstrated
significant interactions between exercise and age, including organic
acids, amino acids, ketones, and keto-acids, which exhibited distinct
responses to exercise in young and older adults. Pre-exercise histidine
and sarcosine were negatively associated with muscle protein synthesis, as
was the pre/post-exercise fold change in plasma histidine. Conclusions:
This study demonstrates that while many exercise-responsive metabolites
change similarly in young and older adults, several demonstrate
age-dependent changes even in the absence of evidence of sarcopenia or
frailty.

【背景】运动所带来的有益健康适应性，源于单次体力活动应答的累积效应。老年人常出现合成代谢抵抗（anabolic resistance）现象：即骨骼肌对运动与营养的合成代谢应答受到削弱。目前，年龄相关合成代谢抵抗的潜在机制正逐步被阐明，但我们对于实际年龄如何影响运动应答的认知仍存在不足。本研究旨在明确健康衰老对单次抗阻训练后外周血代谢组应答的影响，以及循环中是否存在可预测骨骼肌合成代谢应答的代谢物。
【方法】本研究采用横断面研究设计，纳入30名年轻成年人（20~35岁）与49名老年人（65~85岁），涵盖男性与女性。受试者完成单次抗阻训练：以单次最大负重的70%为运动强度，进行8组、每组10次的单侧膝关节伸展训练。分别于运动前、运动即刻以及恢复30、90、180分钟时采集血液样本。采用质子核磁共振波谱法（Proton nuclear magnetic resonance spectroscopy）对各时间点的循环代谢物进行谱图分析。同时采集系列肌肉活检标本，用以检测肌肉蛋白质合成速率。
【结果】本研究分析显示，在33种被检测的血浆代谢物中，单次抗阻训练使其中26种发生显著变化，反映出多项生物学过程的改变。此外，12种代谢物在运动与年龄间存在显著交互作用，包括有机酸、氨基酸、酮体及酮酸，这类代谢物在年轻与老年群体中呈现出截然不同的运动应答特征。运动前的组氨酸与肌氨酸，以及血浆组氨酸的运动前后倍数变化，均与肌肉蛋白质合成呈负相关。
【结论】本研究表明，尽管多数运动应答代谢物在年轻与老年群体中的变化趋势相似，但仍有部分代谢物呈现出年龄依赖性变化，即便受试者未出现肌肉减少症或衰弱的相关证据。