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Statistical mediation of the relationships between chronological age and lipoproteins by nonessential amino acids in healthy men
Computational and Structural Biotechnology Journal ( IF 4.4 ) Pub Date : 2021-11-18 , DOI: 10.1016/j.csbj.2021.11.022 Roger Mallol 1, 2, 3 , Joan Carles Vallvé 4, 5 , Rosa Solà 4, 5 , Josefa Girona 4, 5 , Sven Bergmann 2, 3 , Xavier Correig 5, 6 , Edmond Rock 7 , Brigitte M Winklhofer-Roob 8 , Pere Rehues 4, 5 , Montse Guardiola 4, 5 , Lluís Masana 4, 5 , Josep Ribalta 4, 5
Computational and Structural Biotechnology Journal ( IF 4.4 ) Pub Date : 2021-11-18 , DOI: 10.1016/j.csbj.2021.11.022 Roger Mallol 1, 2, 3 , Joan Carles Vallvé 4, 5 , Rosa Solà 4, 5 , Josefa Girona 4, 5 , Sven Bergmann 2, 3 , Xavier Correig 5, 6 , Edmond Rock 7 , Brigitte M Winklhofer-Roob 8 , Pere Rehues 4, 5 , Montse Guardiola 4, 5 , Lluís Masana 4, 5 , Josep Ribalta 4, 5
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Aging is a major risk factor for metabolic impairment that may lead to age-related diseases such as cardiovascular disease. Different mechanisms that may explain the interplay between aging and lipoproteins, and between aging and low-molecular-weight metabolites (LMWMs), in the metabolic dysregulation associated with age-related diseases have been described separately. Here, we statistically evaluated the possible mediation effects of LMWMs on the relationships between chronological age and lipoprotein concentrations in healthy men ranging from 19 to 75 years of age. Relative and absolute concentrations of LMWMs and lipoproteins, respectively, were assessed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate linear regression and mediation analysis were conducted to explore the associations between age, lipoproteins and LMWMs. The statistical significance of the identified mediation effects was evaluated using the bootstrapping technique, and the identified mediation effects were validated on a publicly available dataset. Chronological age was statistically associated with five lipoprotein classes and subclasses. The mediation analysis showed that serine mediated 24.1% (95% CI: 22.9 – 24.7) of the effect of age on LDL-P, and glutamate mediated 17.9% (95% CI: 17.6 – 18.5) of the effect of age on large LDL-P. In the publicly available data, glutamate mediated the relationship between age and an NMR-derived surrogate of cholesterol. Our results suggest that the age-related increase in LDL particles may be mediated by a decrease in the nonessential amino acid glutamate. Future studies may contribute to a better understanding of the potential biological role of glutamate and LDL particles in aging mechanisms and age-related diseases.
中文翻译：
健康男性非必需氨基酸对实际年龄与脂蛋白关系的统计调节
衰老是代谢损伤的主要危险因素，可能导致心血管疾病等与年龄相关的疾病。在与年龄相关疾病相关的代谢失调中，可以解释衰老与脂蛋白之间以及衰老与低分子量代谢物（LMWM）之间相互作用的不同机制已单独描述。在这里，我们统计评估了 LMWM 对 19 至 75 岁健康男性的实际年龄和脂蛋白浓度之间关系的可能中介作用。通过核磁共振 (NMR) 光谱分别评估 LMWM 和脂蛋白的相对和绝对浓度。进行多元线性回归和中介分析来探讨年龄、脂蛋白和 LMWM 之间的关联。使用引导技术评估所识别的中介效应的统计显着性，并在公开数据集上验证所识别的中介效应。实际年龄与五种脂蛋白类别和亚类有统计相关性。中介分析显示，丝氨酸介导了年龄对 LDL-P 的 24.1% (95% CI: 22.9 – 24.7) 影响，谷氨酸介导了年龄对大 LDL-P 的 17.9% (95% CI: 17.6 – 18.5) 影响-P。在公开的数据中，谷氨酸介导了年龄和核磁共振衍生的胆固醇替代物之间的关系。我们的结果表明，与年龄相关的低密度脂蛋白颗粒增加可能是由非必需氨基酸谷氨酸的减少介导的。未来的研究可能有助于更好地了解谷氨酸和低密度脂蛋白颗粒在衰老机制和年龄相关疾病中的潜在生物学作用。
更新日期：2021-11-18
中文翻译：
健康男性非必需氨基酸对实际年龄与脂蛋白关系的统计调节
衰老是代谢损伤的主要危险因素，可能导致心血管疾病等与年龄相关的疾病。在与年龄相关疾病相关的代谢失调中，可以解释衰老与脂蛋白之间以及衰老与低分子量代谢物（LMWM）之间相互作用的不同机制已单独描述。在这里，我们统计评估了 LMWM 对 19 至 75 岁健康男性的实际年龄和脂蛋白浓度之间关系的可能中介作用。通过核磁共振 (NMR) 光谱分别评估 LMWM 和脂蛋白的相对和绝对浓度。进行多元线性回归和中介分析来探讨年龄、脂蛋白和 LMWM 之间的关联。使用引导技术评估所识别的中介效应的统计显着性，并在公开数据集上验证所识别的中介效应。实际年龄与五种脂蛋白类别和亚类有统计相关性。中介分析显示，丝氨酸介导了年龄对 LDL-P 的 24.1% (95% CI: 22.9 – 24.7) 影响，谷氨酸介导了年龄对大 LDL-P 的 17.9% (95% CI: 17.6 – 18.5) 影响-P。在公开的数据中，谷氨酸介导了年龄和核磁共振衍生的胆固醇替代物之间的关系。我们的结果表明，与年龄相关的低密度脂蛋白颗粒增加可能是由非必需氨基酸谷氨酸的减少介导的。未来的研究可能有助于更好地了解谷氨酸和低密度脂蛋白颗粒在衰老机制和年龄相关疾病中的潜在生物学作用。
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