Cohen Aviv, Weindling Esther, Rabinovich Efrat, Nachman Iftach, Fuchs Shai, Chuartzman Silvia, Gal Lihi, Schuldiner Maya, Bar-Nun Shoshana
Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
PLoS One. 2016 Feb 10;11(2):e0148650. doi: 10.1371/journal.pone.0148650. eCollection 2016.
Transferring Saccharomyces cerevisiae cells to water is known to extend their lifespan. However, it is unclear whether this lifespan extension is due to slowing the aging process or merely keeping old yeast alive. Here we show that in water-transferred yeast, the toxicity of polyQ proteins is decreased and the aging biomarker 47Q aggregates at a reduced rate and to a lesser extent. These beneficial effects of water-transfer could not be reproduced by diluting the growth medium and depended on de novo protein synthesis and proteasomes levels. Interestingly, we found that upon water-transfer 27 proteins are downregulated, 4 proteins are upregulated and 81 proteins change their intracellular localization, hinting at an active genetic program enabling the lifespan extension. Furthermore, the aging-related deterioration of the heat shock response (HSR), the unfolded protein response (UPR) and the endoplasmic reticulum-associated protein degradation (ERAD), was largely prevented in water-transferred yeast, as the activities of these proteostatic network pathways remained nearly as robust as in young yeast. The characteristics of young yeast that are actively maintained upon water-transfer indicate that the extended lifespan is the outcome of slowing the rate of the aging process.
将酿酒酵母细胞转移至水中可延长其寿命。然而，目前尚不清楚这种寿命延长是由于衰老过程减缓，还是仅仅是让衰老的酵母存活下来。在此我们表明，在转移至水中的酵母中，多聚谷氨酰胺蛋白的毒性降低，衰老生物标志物47Q的聚集速率降低且程度减轻。水转移的这些有益效果无法通过稀释生长培养基来重现，并且依赖于从头蛋白质合成和蛋白酶体水平。有趣的是，我们发现水转移后有27种蛋白质表达下调，4种蛋白质表达上调，81种蛋白质改变其细胞内定位，这暗示着存在一个活跃的遗传程序促使寿命延长。此外，热休克反应（HSR）、未折叠蛋白反应（UPR）和内质网相关蛋白降解（ERAD）等与衰老相关的功能衰退在转移至水中的酵母中得到了很大程度的预防，因为这些蛋白质稳态网络途径的活性几乎与年轻酵母中的一样强劲。水转移后积极维持的年轻酵母特征表明，寿命延长是衰老过程速率减缓的结果。
