iBiMED-Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Agra do Crasto, 3810-193 Aveiro, Portugal.
CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
Int J Mol Sci. 2022 May 23;23(10):5830. doi: 10.3390/ijms23105830.
Aging is a complex process which leads to progressive loss of fitness/capability/ability, increasing susceptibility to disease and, ultimately, death. Regardless of the organism, there are some features common to aging, namely, the loss of proteostasis and cell senescence. Mammalian cell lines have been used as models to study the aging process, in particular, cell senescence. Thus, the aim of this study was to characterize the senescence-associated metabolic profile of a long-term culture of human fibroblasts using Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. We sub-cultivated fibroblasts from a newborn donor from passage 4 to passage 17 and the results showed deep changes in the spectroscopic profile of cells over time. Late passage cells were characterized by a decrease in the length of fatty acid chains, triglycerides and cholesterol and an increase in lipid unsaturation. We also found an increase in the content of intermolecular β-sheets, possibly indicating an increase in protein aggregation levels in cells of later passages. Metabolic profiling by NMR showed increased levels of extracellular lactate, phosphocholine and glycine in cells at later passages. This study suggests that spectroscopy approaches can be successfully used to study changes concomitant with cell senescence and validate the use of human fibroblasts as a model to monitor the aging process.
衰老是一个复杂的过程，导致适应性/能力逐渐丧失，增加患病的易感性，最终导致死亡。无论生物体如何，衰老都有一些共同的特征，即蛋白质稳态的丧失和细胞衰老。哺乳动物细胞系已被用作研究衰老过程的模型，特别是细胞衰老。因此，本研究旨在使用傅里叶变换红外和核磁共振波谱法对人成纤维细胞的长期培养物的衰老相关代谢特征进行表征。我们从小儿供体的第 4 代培养至第 17 代，结果表明细胞的光谱特征随时间发生了深刻变化。晚期传代细胞的特征是脂肪酸链、甘油三酯和胆固醇长度减少，脂质不饱和度增加。我们还发现细胞间β-折叠含量增加，可能表明晚期传代细胞中蛋白质聚集水平增加。NMR 代谢组学显示，晚期传代细胞中细胞外乳酸盐、磷酸胆碱和甘氨酸的含量增加。这项研究表明，光谱学方法可成功用于研究与细胞衰老相关的变化，并验证使用人成纤维细胞作为监测衰老过程的模型的有效性。
