Rudzińska Magdalena, Parodi Alessandro, Balakireva Anastasia V, Chepikova Olga E, Venanzi Franco M, Zamyatnin Andrey A
Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
Antioxidants (Basel). 2020 Jan 22;9(2):94. doi: 10.3390/antiox9020094.
Different molecular signaling pathways, biological processes, and intercellular communication mechanisms control longevity and are affected during cellular senescence. Recent data have suggested that organelle communication, as well as genomic and metabolic dysfunctions, contribute to this phenomenon. Oxidative stress plays a critical role by inducing structural modifications to biological molecules while affecting their function and catabolism and eventually contributing to the onset of age-related dysfunctions. In this scenario, proteins are not adequately degraded and accumulate in the cell cytoplasm as toxic aggregates, increasing cell senescence progression. In particular, carbonylation, defined as a chemical reaction that covalently and irreversibly modifies proteins with carbonyl groups, is considered to be a significant indicator of protein oxidative stress and aging. Here, we emphasize the role and dysregulation of the molecular pathways controlling cell metabolism and proteostasis, the complexity of the mechanisms that occur during aging, and their association with various age-related disorders. The last segment of the review details current knowledge on protein carbonylation as a biomarker of cellular senescence in the development of diagnostics and therapeutics for age-related dysfunctions.
不同的分子信号通路、生物过程和细胞间通讯机制控制着寿命，并在细胞衰老过程中受到影响。最近的数据表明，细胞器通讯以及基因组和代谢功能障碍促成了这一现象。氧化应激通过诱导生物分子的结构修饰，同时影响其功能和分解代谢，最终导致与年龄相关的功能障碍的发生，从而发挥关键作用。在这种情况下，蛋白质不能被充分降解，并作为有毒聚集体在细胞质中积累，加速细胞衰老进程。特别是，羰基化被定义为一种用羰基对蛋白质进行共价且不可逆修饰的化学反应，被认为是蛋白质氧化应激和衰老的重要指标。在这里，我们强调控制细胞代谢和蛋白质稳态的分子途径的作用和失调、衰老过程中发生的机制的复杂性，以及它们与各种与年龄相关的疾病的关联。综述的最后一部分详细介绍了目前关于蛋白质羰基化作为细胞衰老生物标志物在与年龄相关功能障碍的诊断和治疗开发中的知识。
