Department of Health Sciences Research, Mayo Clinic Rochester, Minnesota.
Department of Physical Medicine and Rehabilitation, Mayo Clinic Rochester, Minnesota.
J Gerontol A Biol Sci Med Sci. 2018 Jun 14;73(7):960-965. doi: 10.1093/gerona/glx139.
Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function.
We examined the cross-sectional association between plasma ceramides, sphingosine-1-phosphate (S1P), and ceramide/S1P ratios and gait, a robust measure of physical function, in 340 clinically normal participants aged 70 years and older enrolled in the Mayo Clinic Study of Aging. GAITRite® instrumentation was used to measure gait speed, cadence, step width, double support time, and intra-individual stride time variability. Based on previous studies, we hypothesized that higher plasma levels of ceramide C16:0 would be associated with worse gait.
Multivariable adjusted linear regression models revealed that higher levels of ceramide C16:0 were associated with slower gait speed, decreased cadence, and increased double support time.
These results suggest an association between plasma ceramide C16:0 and physical function. Longitudinal studies are needed to determine whether elevated ceramide C16:0 can be utilized as a prognostic marker for functional decline.
步态紊乱与虚弱、残疾和死亡风险增加有关，但因果分子途径尚不清楚。神经酰胺等神经鞘脂与多种与年龄相关的疾病有关。神经酰胺在细胞和动物模型中促进萎缩、坏死和蛋白水解，并且男性的神经酰胺 C16:0 水平与肌肉质量呈负相关。然而，检查神经鞘脂和身体功能的证据很少。
我们在梅奥诊所老龄化研究中检查了 340 名年龄在 70 岁及以上的临床正常参与者的血浆神经酰胺、鞘氨醇-1-磷酸 (S1P) 和神经酰胺/S1P 比值与步态（身体功能的可靠测量）之间的横断面关联。GAITRite® 仪器用于测量步态速度、步频、步宽、双支撑时间和个体内步时变异性。基于先前的研究，我们假设更高的血浆神经酰胺 C16:0 水平与更差的步态有关。
多变量调整线性回归模型显示，更高水平的神经酰胺 C16:0 与较慢的步态速度、降低的步频和增加的双支撑时间有关。
这些结果表明血浆神经酰胺 C16:0 与身体功能之间存在关联。需要进行纵向研究以确定升高的神经酰胺 C16:0 是否可用作功能下降的预后标志物。
