Jamshidi Neema, Xu Xiuling, von Löhneysen Katharina, Soldau Katrin, Mohney Rob P, Karoly Edward D, Scott Mike, Friedman Jeffrey S
University of California, San Diego, Institute of Engineering in Medicine, La Jolla, CA, USA.
University of California, Los Angeles, Department of Radiological Sciences, Los Angeles, CA, USA.
iScience. 2020 Sep 29;23(10):101630. doi: 10.1016/j.isci.2020.101630. eCollection 2020 Oct 23.
Understanding the mechanisms for cellular aging is a fundamental question in biology. Normal red blood cells (RBCs) survive for approximately 100 days, and their survival is likely limited by functional decline secondary to cumulative damage to cell constituents, which may be reflected in altered metabolic capabilities. To investigate metabolic changes during RBC aging, labeled cell populations were purified at intervals and assessed for abundance of metabolic intermediates using mass spectrometry. A total of 167 metabolites were profiled and quantified from cell populations of defined ages. Older RBCs maintained ATP and redox charge states at the cost of altered activity of enzymatic pathways. Time-dependent changes were identified in metabolites related to maintenance of the redox state and membrane structure. These findings illuminate the differential metabolic pathway usage associated with normal cellular aging and identify potential biomarkers to determine average RBC age and rates of RBC turnover from a single blood sample.
了解细胞衰老的机制是生物学中的一个基本问题。正常红细胞（RBC）存活约100天，其存活可能受细胞成分累积损伤继发的功能衰退限制，这可能反映在代谢能力改变上。为研究红细胞衰老过程中的代谢变化，每隔一段时间纯化标记的细胞群体，并使用质谱法评估代谢中间体的丰度。从特定年龄的细胞群体中总共分析和定量了167种代谢物。衰老的红细胞以改变酶促途径活性为代价维持ATP和氧化还原电荷状态。在与氧化还原状态维持和膜结构相关的代谢物中发现了随时间的变化。这些发现阐明了与正常细胞衰老相关的不同代谢途径使用情况，并确定了潜在的生物标志物，以从单一血样中确定红细胞的平均年龄和红细胞周转率。
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