Mack Till Georg Alexander, Kreis Patricia, Eickholt Britta Johanna
Biol Chem. 2016 Mar;397(3):223-9. doi: 10.1515/hsz-2015-0185.
Ageing is a complex deteriorating process that coincides with changes in metabolism, replicative senescence, increased resistance to apoptosis, as well as progressive mitochondria dysfunction that lead to an increase production and accumulation of reactive oxygen species (ROS). Although controversy on the paradigm of the oxidative damage theory of ageing exists, persuasive studies in Caenorhabditis elegans and yeast have demonstrated that manipulation of ROS can modify the process of ageing and influences the damage of proteins, lipids and DNA. In neurons, ageing impacts on the intrinsic neuronal excitability, it decreases the size of neuronal soma and induces the loss of dendrites and dendritic spines. The actin cytoskeleton is an abundant and broadly expressed system that plays critical functions in many cellular processes ranging from cell motility to controlling cell shape and polarity. It is thus hardly surprising that the expression and the function of actin in neurons is crucial for the morphological changes that occur in the brain throughout life. We propose that alterations in actin filament dynamics in dendritic spines may be one of the key events contributing to the initial phases of ageing in the brain.
衰老过程是一个复杂的退化过程，与新陈代谢的变化、复制性衰老、对细胞凋亡的抵抗力增加以及线粒体功能的逐渐失调同时发生，而线粒体功能失调会导致活性氧（ROS）的产生和积累增加。尽管关于衰老的氧化损伤理论范式存在争议，但在秀丽隐杆线虫和酵母中的有说服力的研究表明，对ROS的调控可以改变衰老过程，并影响蛋白质、脂质和DNA的损伤。在神经元中，衰老会影响神经元的内在兴奋性，减小神经元胞体的大小，并导致树突和树突棘的丢失。肌动蛋白细胞骨架是一个丰富且广泛表达的系统，在从细胞运动到控制细胞形状和极性的许多细胞过程中发挥着关键作用。因此，肌动蛋白在神经元中的表达和功能对于大脑一生中发生的形态变化至关重要，这一点不足为奇。我们认为，树突棘中肌动蛋白丝动力学的改变可能是导致大脑衰老初始阶段的关键事件之一。
