Hwang Jung Sun, Hwang Jae Sung, Chang Ihseop, Kim Sujong
Skin Research Institute, Amorepacific Corporation, R&D Center, Gyeonggi-do, South Korea.
J Gerontol A Biol Sci Med Sci. 2007 May;62(5):490-9. doi: 10.1093/gerona/62.5.490.
We measured proteasome activities and the levels of proteasome subunits in dermal fibroblasts from individuals aged 20-82 years. Proteasome activities changed with age in a biphasic manner, decreasing significantly up to 50 years of age and showing no significant change between 50 and 78 years of age. Similarly, proteasome activities in replicatively senescent dermal fibroblasts showed a passage-dependent biphasic change. We confirmed that the decreases in proteasome activities were accompanied by the accumulation of oxidized and ubiquitinated proteins. The decline in proteasome activities in aging fibroblasts was associated with a decrease in the expression of proteasome subunits. We found that the restoration of the normal level of proteasome catalytic subunits, using a lentivirus gene-delivery system, decreased the severity of the aging markers in dermal fibroblasts from elderly donors. These findings suggest that proteasome malfunction may contribute to the aging process in human skin and that the maintenance of normal proteasome activities could delay skin aging.
我们检测了20至82岁个体皮肤成纤维细胞中的蛋白酶体活性及蛋白酶体亚基水平。蛋白酶体活性随年龄呈双相变化，在50岁之前显著下降，在50至78岁之间无显著变化。同样，复制性衰老的皮肤成纤维细胞中的蛋白酶体活性也呈现出与传代相关的双相变化。我们证实，蛋白酶体活性的降低伴随着氧化蛋白和泛素化蛋白的积累。衰老成纤维细胞中蛋白酶体活性的下降与蛋白酶体亚基表达的减少有关。我们发现，使用慢病毒基因递送系统恢复蛋白酶体催化亚基的正常水平，可降低老年供体皮肤成纤维细胞中衰老标志物的严重程度。这些发现表明，蛋白酶体功能障碍可能导致人类皮肤衰老，维持正常的蛋白酶体活性可能延缓皮肤衰老。
