Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, 1105 AZ, Amsterdam, The Netherlands.
Sci Rep. 2017 May 25;7(1):2408. doi: 10.1038/s41598-017-02539-w.
Abnormal nutrient metabolism is a hallmark of aging, and the underlying genetic and nutritional framework is rapidly being uncovered, particularly using C. elegans as a model. However, the direct metabolic consequences of perturbations in life history of C. elegans remain to be clarified. Based on recent advances in the metabolomics field, we optimized and validated a sensitive mass spectrometry (MS) platform for identification of major metabolite classes in worms and applied it to study age and diet related changes. Using this platform that allowed detection of over 600 metabolites in a sample of 2500 worms, we observed marked changes in fatty acids, amino acids and phospholipids during worm life history, which were independent from the germ-line. Worms underwent a striking shift in lipid metabolism after early adulthood that was at least partly controlled by the metabolic regulator AAK-2/AMPK. Most amino acids peaked during development, except aspartic acid and glycine, which accumulated in aged worms. Dietary intervention also influenced worm metabolite profiles and the regulation was highly specific depending on the metabolite class. Altogether, these MS-based methods are powerful tools to perform worm metabolomics for aging and metabolism-oriented studies.
异常的营养代谢是衰老的一个标志，其潜在的遗传和营养基础正在被迅速揭示，特别是使用秀丽隐杆线虫作为模型。然而，秀丽隐杆线虫生活史干扰的直接代谢后果仍有待阐明。基于代谢组学领域的最新进展，我们优化并验证了一种用于鉴定线虫主要代谢物类别的灵敏质谱（MS）平台，并将其应用于研究年龄和饮食相关的变化。使用该平台可以在 2500 条线虫的样本中检测到超过 600 种代谢物，我们观察到在线虫的生活史中，脂肪酸、氨基酸和磷脂发生了显著变化，这些变化与生殖系无关。线虫在成年早期经历了明显的脂质代谢转变，至少部分受到代谢调节剂 AAK-2/AMPK 的控制。除了天冬氨酸和甘氨酸外，大多数氨基酸在发育过程中达到峰值，而天冬氨酸和甘氨酸在老年线虫中积累。饮食干预也会影响线虫的代谢物谱，而且这种调节具有高度的特异性，取决于代谢物类别。总的来说，这些基于 MS 的方法是进行衰老和代谢为导向的线虫代谢组学研究的有力工具。
