Katsiki Magda, Chondrogianni Niki, Chinou Ioanna, Rivett A Jennifer, Gonos Efstathios S
Institute of Biological Research and Biotechnology, Laboratory of Molecular and Cellular Aging, National Hellenic Research Foundation, Athens, Greece.
Rejuvenation Res. 2007 Jun;10(2):157-72. doi: 10.1089/rej.2006.0513.
Normal human fibroblasts undergo replicative senescence due to both genetic and environmental factors. Senescence and aging can be further accelerated by exposure of cells to a variety of oxidative agents that contribute among other effects to the accumulation of damaged proteins. The proteasome, a multicatalytic nonlysosomal protease, has impaired function during aging, while its increased expression delays senescence in human fibroblasts. The aim of this study was to identify natural compounds that enhance proteasome activity and exhibit antiaging properties. We demonstrate that oleuropein, the major constituent of Olea europea leaf extract, olive oil and olives, enhances the proteasome activities in vitro stronger than other known chemical activators, possibly through conformational changes of the proteasome. Moreover, continuous treatment of early passage human embryonic fibroblasts with oleuropein decreases the intracellular levels of reactive oxygen species (ROS), reduces the amount of oxidized proteins through increased proteasome-mediated degradation rates and retains proteasome function during replicative senescence. Importantly, oleuropein-treated cultures exhibit a delay in the appearance of senescence morphology and their life span is extended by approximately 15%. In summary, these data demonstrate the beneficial effect of oleuropein on human fibroblasts undergoing replicative senescence and provide new insights towards enhancement of cellular antioxidant mechanisms by natural compounds that can be easily up-taken through normal diet.
由于遗传和环境因素，正常人类成纤维细胞会经历复制性衰老。细胞暴露于多种氧化剂中会进一步加速衰老，这些氧化剂除其他作用外，还会导致受损蛋白质的积累。蛋白酶体是一种多催化非溶酶体蛋白酶，在衰老过程中功能受损，而其表达增加可延缓人类成纤维细胞的衰老。本研究的目的是鉴定能增强蛋白酶体活性并具有抗衰老特性的天然化合物。我们证明，橄榄苦苷（油橄榄叶提取物、橄榄油和橄榄中的主要成分）在体外比其他已知化学激活剂更能增强蛋白酶体活性，可能是通过蛋白酶体的构象变化实现的。此外，用橄榄苦苷持续处理早期传代的人类胚胎成纤维细胞可降低细胞内活性氧（ROS）水平，通过提高蛋白酶体介导的降解速率减少氧化蛋白的数量，并在复制性衰老过程中保持蛋白酶体功能。重要的是，经橄榄苦苷处理的培养物衰老形态出现延迟，其寿命延长约15%。总之，这些数据证明了橄榄苦苷对经历复制性衰老的人类成纤维细胞的有益作用，并为通过正常饮食易于摄取的天然化合物增强细胞抗氧化机制提供了新的见解。
