Kang Yi, Tang Yidan, Kong Weishuang, Zhu Tao, Chen Guo
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Front Endocrinol (Lausanne). 2024 Dec 23;15:1404308. doi: 10.3389/fendo.2024.1404308. eCollection 2024.
Evidence indicates a negative link between glucosamine and age-related cognitive decline and sarcopenia. However, the causal relationship remains uncertain. This study aims to verify whether glucosamine is causally associated with cognitive function and sarcopenia.
Forty-eight genetic variants linked to glucosamine use were extracted from the MRC-IEU consortium. Besides, we gathered cognition proxy indicators [cognitive performance and fluid intelligence score (FIS)], and sarcopenia-related indicators, namely, appendicular lean mass (ALM), whole body fat-free mass (WBFM), low hand grip strength, facial aging (FA), moderate to vigorous physical activity levels, usual walking pace and DNA methylation GrimAge acceleration from the large publicly available genome-wide association studies. Initially, Mendelian randomization (MR) analyses were conducted to ascertain the causal impact of glucosamine on cognition and sarcopenia-related traits. Subsequently, the two-step MR and multivariable MR (MVMR) were employed to examine whether any mediators causally mediated the observed associations.
MR analysis indicated that glucosamine was associated with increased cognitive performance ( = 8.46E-04), FIS ( = 7.50E-04), ALM ( = 6.45E-08), WBFM ( = 1.97E-03), usual walking pace ( = 2.55E-07), and moderate to vigorous physical activity levels ( = 3.29E-03), but associated with decreased FA risk ( = 3.77E-05) and DNA methylation GrimAge acceleration ( = 0.001). However, there were no significant causal associations between glucosamine and low hand grip strength. Multivariable MR showed that glucosamine continued to have a significant effect on cognitive performance, FIS, ALM, WBFM, usual walking pace, and moderate to vigorous physical activity levels after controlling for osteoarthritis (OA) and body mass index (BMI) ( < 0.05). We further found that C-reactive protein levels (CRP) may mediate the association of glucosamine and ALM, WBFM, usual walking pace, and physical activity (p < 0.05), and basal metabolic rate (BMR) may mediate the association of glucosamine and cognitive performance, FIS, ALM, WBFM, and usual walking pace ( < 0.05).
Regular glucosamine use enhances cognitive function and postpones sarcopenia for preserving the functional capacities necessary, and the impact of glucosamine on cognition and sarcopenia could be partially attributed to the mediation of BMR and CRP.
有证据表明氨基葡萄糖与年龄相关的认知衰退和肌肉减少症之间存在负相关。然而，因果关系仍不确定。本研究旨在验证氨基葡萄糖是否与认知功能和肌肉减少症存在因果关联。
从MRC-IEU联盟中提取了48个与氨基葡萄糖使用相关的基因变异。此外，我们从大型公开的全基因组关联研究中收集了认知替代指标[认知表现和流体智力得分（FIS）]以及与肌肉减少症相关的指标，即四肢瘦体重（ALM）、全身去脂体重（WBFM）、低握力、面部衰老（FA）、中度至剧烈身体活动水平、通常步行速度和DNA甲基化GrimAge加速。最初，进行孟德尔随机化（MR）分析以确定氨基葡萄糖对认知和与肌肉减少症相关性状的因果影响。随后，采用两步MR和多变量MR（MVMR）来检验是否有任何中介因素因果介导了观察到的关联。
MR分析表明，氨基葡萄糖与认知表现增加（=8.46E-04）、FIS（=7.50E-04）、ALM（=6.45E-08）、WBFM（=1.97E-03）、通常步行速度（=2.55E-07）以及中度至剧烈身体活动水平（=3.29E-03）相关，但与FA风险降低（=3.77E-05）和DNA甲基化GrimAge加速降低（=0.001）相关。然而，氨基葡萄糖与低握力之间没有显著的因果关联。多变量MR显示，在控制骨关节炎（OA）和体重指数（BMI）后，氨基葡萄糖对认知表现、FIS、ALM、WBFM、通常步行速度和中度至剧烈身体活动水平仍有显著影响（<0.05）。我们进一步发现，C反应蛋白水平（CRP）可能介导氨基葡萄糖与ALM、WBFM、通常步行速度和身体活动之间的关联（p<0.05），基础代谢率（BMR）可能介导氨基葡萄糖与认知表现、FIS、ALM、WBFM和通常步行速度之间的关联（<0.05）。
定期使用氨基葡萄糖可增强认知功能并延缓肌肉减少症，以维持必要的功能能力，氨基葡萄糖对认知和肌肉减少症的影响可能部分归因于BMR和CRP的介导作用。
