Shah Arman Ali, Liu Binghua, Tang Zhihuai, Wang Wang, Yang Wenjie, Hu Quanjun, Liu Yan, Zhang Nianhui, Liu Ke
Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, Sichuan, China.
Aging (Albany NY). 2021 Mar 19;13(7):9859-9873. doi: 10.18632/aging.202738.
Previous studies demonstrated that lifelong treatment with a slow HS releasing donor extends yeast chronological lifespan (CLS), but it is not clear when the action of HS benefits to CLS during yeast growth. Here, we show that short HS treatments by using NaHS as a fast HS releasing donor at 96 hours after inoculation extended yeast CLS while NaHS treatments earlier than 72 hours after inoculation failed to do so. To reveal the mechanism, we analyzed the transcriptome of yeast cells with or without the early and late NaHS treatments. We found that both treatments had similar effects on pathways related to CLS regulation. Follow-up qPCR and ROS analyses suggest that altered expression of some antioxidant genes by the early NaHS treatments were not stable enough to benefit CLS. Moreover, transcriptome data also indicated that some genes were regulated differently by the early and late HS treatment. Specifically, we found that the expression of , a human homolog and also a key regulator of the yeast cell wall synthesis, was significantly altered by the late NaHS treatment but not altered by the early NaHS treatment. Finally, the key role of in CLS regulation by HS is revealed by CLS data showing that the late NaHS treatment did not enhance the CLS of a knockout mutant. This study sheds light on the molecular mechanism of CLS extension induced by HS, and for the first time addresses the importance of HS treatment timing for lifespan extension.
先前的研究表明，用缓慢释放硫化氢的供体进行终身治疗可延长酵母的时序寿命（CLS），但尚不清楚硫化氢在酵母生长过程中对CLS产生作用的时间。在此，我们表明，在接种后96小时使用硫氢化钠（NaHS）作为快速释放硫化氢的供体进行短期硫化氢处理可延长酵母的CLS，而在接种后72小时之前进行NaHS处理则无法达到此效果。为了揭示其机制，我们分析了经过早期和晚期NaHS处理以及未处理的酵母细胞的转录组。我们发现这两种处理对与CLS调节相关的通路具有相似的影响。后续的定量聚合酶链反应（qPCR）和活性氧（ROS）分析表明，早期NaHS处理导致的一些抗氧化基因表达变化不够稳定，无法对CLS产生有益影响。此外，转录组数据还表明，一些基因在早期和晚期硫化氢处理下受到的调控有所不同。具体而言，我们发现，作为人类同源物且也是酵母细胞壁合成关键调节因子的[具体基因名称未给出]的表达在晚期NaHS处理后发生了显著变化，但在早期NaHS处理后未发生变化。最后，CLS数据表明晚期NaHS处理并未增强[具体基因名称未给出]敲除突变体的CLS，从而揭示了[具体基因名称未给出]在硫化氢对CLS调节中的关键作用。这项研究揭示了硫化氢诱导CLS延长的分子机制，并首次阐明了硫化氢处理时间对寿命延长的重要性。
