Girasole Marco, Dinarelli Simone, Longo Giovanni
Biotech@ISM, Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche, Rome, Italy.
Front Microbiol. 2023 Jun 2;14:1196764. doi: 10.3389/fmicb.2023.1196764. eCollection 2023.
Red blood cells (RBCs) are among the simplest, yet physiologically relevant biological specimens, due to their peculiarities, such as their lack of nucleus and simplified metabolism. Indeed, erythrocytes can be seen as biochemical machines, capable of performing a limited number of metabolic pathways. Along the aging path, the cells' characteristics change as they accumulate oxidative and non-oxidative damages, and their structural and functional properties degrade.
In this work, we have studied RBCs and the activation of their ATP-producing metabolism using a real-time nanomotion sensor. This device allowed time-resolved analyses of the activation of this biochemical pathway, measuring the characteristics and the timing of the response at different points of their aging and the differences observed in favism erythrocytes in terms of the cellular reactivity and resilience to aging. Favism is a genetic defect of erythrocytes, which affects their ability to respond to oxidative stresses but that also determines differences in the metabolic and structural characteristic of the cells.
Our work shows that RBCs from favism patients exhibit a different response to the forced activation of the ATP synthesis compared to healthy cells. In particular, the favism cells, compared to healthy erythrocytes, show a greater resilience to the aging-related insults which was in good accord with the collected biochemical data on ATP consumption and reload.
This surprisingly higher endurance against cell aging can be addressed to a special mechanism of metabolic regulation that permits lower energy consumption in environmental stress conditions.
红细胞（RBCs）是最简单但具有生理相关性的生物样本之一，因其具有独特之处，如缺乏细胞核且代谢简化。实际上，红细胞可被视为生化机器，能够执行有限数量的代谢途径。在衰老过程中，随着细胞积累氧化和非氧化损伤，其特性会发生变化，结构和功能属性也会退化。
在这项工作中，我们使用实时纳米运动传感器研究了红细胞及其产生ATP的代谢激活情况。该设备能够对这一生化途径的激活进行时间分辨分析，测量其在不同衰老阶段的反应特征和时间，以及在蚕豆病红细胞中观察到的细胞反应性和抗老化能力的差异。蚕豆病是红细胞的一种遗传缺陷，它影响红细胞对氧化应激的反应能力，但也决定了细胞代谢和结构特征的差异。
我们的研究表明，与健康细胞相比，蚕豆病患者的红细胞对ATP合成的强制激活表现出不同的反应。特别是，与健康红细胞相比，蚕豆病细胞对与衰老相关的损伤表现出更大的恢复能力，这与收集到的关于ATP消耗和重新加载的生化数据高度一致。
这种对细胞衰老出人意料的更高耐受性可归因于一种特殊的代谢调节机制，该机制允许在环境应激条件下降低能量消耗。
