Department of Nutritional Toxicology, Friedrich Schiller University Jena, Dornburger Str. 24, 07743 Jena, Germany.
Curr Pharm Des. 2014;20(18):3040-51. doi: 10.2174/13816128113196660709.
A number of studies reported a relation between longevity, oxidative stress and age-related diseases. Every aerobic organism is inevitably exposed to a permanent flux of free radicals and oxidants. Due to the limited activity of antioxidant and repair mechanisms, levels of reactive oxygen species can increase during aging. Protein damage caused by elevated levels of free radicals or oxidants has an important influence on cellular viability and leads to malfunction of proteins in aged cells. In addition, modified and impaired proteins can cross-link and form the bases of many senescence-associated alterations and also of neurodegenerative diseases. To ensure the maintenance of normal cellular functions, eukaryotic cells exert proteolysis through two systems: the proteasomal system and the lysosomal system, which is degrading cellular components after autophagy. During cellular differentiation and aging, both systems are subject to extensive changes that significantly affect their proteolytic activity. It has been suggested that highly modified proteins and undegradable protein aggregates also affect the intracellular proteolytic systems. Therefore, it is essential to understand the relationship between protein oxidation, intracellular proteolytic systems and cellular defence mechanisms.
许多研究报告指出，长寿、氧化应激与年龄相关疾病之间存在关联。每个需氧生物都会不可避免地受到自由基和氧化剂的持续影响。由于抗氧化和修复机制的活性有限，活性氧的水平会在衰老过程中增加。自由基或氧化剂水平升高导致的蛋白质损伤对细胞活力有重要影响，并导致衰老细胞中蛋白质的功能失调。此外，经过修饰和受损的蛋白质可以交联并形成许多与衰老相关的改变以及神经退行性疾病的基础。为了确保正常细胞功能的维持，真核细胞通过两种系统进行蛋白质水解：蛋白酶体系统和溶酶体系统，后者在自噬后降解细胞成分。在细胞分化和衰老过程中，这两个系统都发生了广泛的变化，这显著影响了它们的蛋白水解活性。有人认为，高度修饰的蛋白质和不可降解的蛋白质聚集体也会影响细胞内蛋白水解系统。因此，了解蛋白质氧化、细胞内蛋白水解系统和细胞防御机制之间的关系至关重要。
