Ubaida-Mohien Ceereena, Moaddel Ruin, Spendiff Sally, MacMillan Norah J, Filion Marie-Eve, Morais Jose A, Candia Julián, Fitzgerald Liam F, Taivassalo Tanja, Coen Paul M, Ferrucci Luigi, Hepple Russell T
Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.
Aging Cell. 2025 Mar 10;24(5):e70002. doi: 10.1111/acel.70002.
Physical function declines with aging, yet there is considerable heterogeneity, with some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical function with aging, we performed proteomics, targeted metabolomics, and targeted kynurenine-focused metabolomic analyses on serum specimens from three groups of octogenarians: High-functioning master athletes (HF, n = 16), healthy normal-functioning non-athletes (NF, n = 12), and lower functioning non-athletes (LF, n = 11). Higher performance status was associated with evidence consistent with: Lower levels of circulating proinflammatory markers, as well as unperturbed tryptophan metabolism, with the normal function of the kynurenic pathway; higher circulating levels of lysophosphatidylcholines that have been previously associated with better mitochondrial oxidative capacity; lower activity of the integrated stress response; lower levels of circulating SASP protein members; and lower levels of proteins that reflect neurodegeneration/denervation. Extending the observations of previous studies focused on the biomarkers of aging that predict poor function, our findings show that many of the same biomarkers associated with poor function exhibit attenuated changes in those who maintain a high function. Because of the cross-sectional nature of this study, results should be interpreted with caution, and bidirectional causality, where physical activity behavior is both a cause and outcome of differences in the biomarker changes, remains a possible interpretation.
身体功能会随着年龄增长而下降，但存在相当大的个体差异，有些人功能下降非常缓慢，而另一些人则经历加速的功能衰退。为了深入了解促进老年人保持高身体功能的机制，我们对三组八旬老人的血清样本进行了蛋白质组学、靶向代谢组学以及以犬尿氨酸为重点的靶向代谢组学分析：高功能的老年运动员（HF，n = 16）、健康的功能正常的非运动员（NF，n = 12）以及功能较低的非运动员（LF，n = 11）。较高的身体功能状态与以下证据相关：循环促炎标志物水平较低，色氨酸代谢未受干扰，犬尿氨酸途径功能正常；循环中溶血磷脂酰胆碱水平较高，此前已发现其与更好的线粒体氧化能力相关；综合应激反应活性较低；循环中衰老相关分泌表型（SASP）蛋白成员水平较低；以及反映神经退行性变/失神经支配的蛋白质水平较低。扩展先前关于预测功能不佳的衰老生物标志物的研究观察结果，我们的研究结果表明，许多与功能不佳相关的相同生物标志物在保持高功能的人群中变化减弱。由于本研究的横断面性质，结果应谨慎解释，并且身体活动行为既是生物标志物变化差异的原因又是结果的双向因果关系仍然是一种可能的解释。
