Nowotny Kerstin, Jung Tobias, Grune Tilman, Höhn Annika
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
Exp Gerontol. 2014 Sep;57:122-31. doi: 10.1016/j.exger.2014.05.016. Epub 2014 May 28.
Increasing cellular damage during the aging process is considered to be one factor limiting the lifespan of organisms. Besides the DNA and lipids, proteins are frequent targets of non-enzymatic modifications by reactive substances including oxidants and glycating agents. Non-enzymatic protein modifications may alter the protein structure often leading to impaired functionality. Although proteolytic systems ensure the removal of modified proteins, the activity of these proteases was shown to decline during the aging process. The additional age-related increase of reactive compounds as a result of impaired antioxidant systems leads to the accumulation of damaged proteins and the formation of protein aggregates. Both, non-enzymatic modified proteins and protein aggregates impair cellular functions and tissue properties by a variety of mechanisms. This is increasingly important in aging and age-related diseases. In this review, we will give an overview on oxidation and glycation of proteins and the function of modified proteins in aggregate formation. Furthermore, their effects as well as their role in aging and age-related diseases will be highlighted.
衰老过程中细胞损伤的增加被认为是限制生物体寿命的一个因素。除了DNA和脂质外，蛋白质也是包括氧化剂和糖化剂在内的活性物质进行非酶修饰的常见靶点。非酶蛋白质修饰可能会改变蛋白质结构，常常导致功能受损。尽管蛋白水解系统可确保清除修饰后的蛋白质，但这些蛋白酶的活性在衰老过程中会下降。抗氧化系统受损导致与年龄相关的活性化合物额外增加，从而导致受损蛋白质的积累和蛋白质聚集体的形成。非酶修饰的蛋白质和蛋白质聚集体都会通过多种机制损害细胞功能和组织特性。这在衰老和与年龄相关的疾病中越来越重要。在这篇综述中，我们将概述蛋白质的氧化和糖化以及修饰后的蛋白质在聚集体形成中的作用。此外，还将重点介绍它们的影响以及它们在衰老和与年龄相关疾病中的作用。
