基于代谢组学技术分析年龄对健康人血清和尿液代谢物的影响

Metabonomic investigation of effects of age on metabolic profile in healthy human serum and urine

目的 利用代谢组学技术研究不同年龄段健康人的代谢表型和生化组成差异. 方法 采用气相色谱-质谱联用仪（GC/MS）对37例健康青年人和19例健康中老年人的血清和尿样中内源性小分子代谢物进行全面检测,利用多变量数据分析和方差分析方法分析两组间差异. 结果 两组在偏最小二乘-判别式分析（PLS-DA）得分图中可直观清晰地分簇,且得分图参数与年龄呈线性相关.血清和尿样中与年龄相关的代谢物及变化趋势有相同之处也有各自的特性,中老年人血清中大部分代谢物较青年人血清中降低,两组间差异有统计学意义,并鉴定出结构的化合物为32个（5个,P＜0.05;27个,P＜0.01）,而尿液中代谢物均升高,两组间差异有统计学意义,并鉴定出结构的化合物为29个（3个,P＜0.05;26个,P＜0.01）,其中部分代谢物与临床常规实验室检查指标呈线性相关.生化代谢通路分析发现年龄相关的代谢物涉及氨基酸代谢、糖代谢、脂代谢、核苷酸代谢、三羧酸循环、肌醇代谢等,还与氧化应激相关. 结论 代谢组学技术是探索年龄相关人类特征代谢谱的有前景的工具,也为进一步研究疾病发展的生物学本质和药物治疗作用奠定基础.

Objective To investigate the metabolic phenotype or biochemical compositionvariations of healthy subjects across age groups by metabonomics.Methods Endogenous metabolites in serum and urine were comprehensively detected by gas chromatography/ mass spectrometry （GC/MS） in two groups of 37 healthy young subjects versus 19 healthy elderly subjects, and their difference between the two groups was analyzed by multivariate statistical technique and MANOVA.Results The two groups were visually clustered in partial least squares projection to latent structures and discriminant analysis（PLS-DA） scores plots, and the linear correlation between the parameters of the scores plot and age were observed.Age-related metabolites and their variation tendency in serum and urine had homogeneity and their own characteristics.Most metabolites in sera were decreased in elderly subjects as compared with young subjects （P〈0.05）.However, all metabolites in urine of healthy elderly subjects were increased （P〈0.05）.Additionally, parts of these metabolites were linear related with indexes of clinical routine laboratory examination.Biochemical metabolic pathway analysis indicated that age-related metabolites were involved in amino acid metabolism, saccharometabolism, lipid metabolism, nucleoside metabolism, tricarboxylic acid cycle,inositol metabolism, etcetera, and were in relationship with oxidative stress.Conclusions Metabonomics may be a promising tool to investigate the age-related characteristic metabolic profile of human,and also could lay the foundations for further study on the biological nature of disease development and on pharmacodynamic action of drugs.