TOR1-Mediated Control of Lifespan Genes: Insights from Saccharomyces cerevisiae

This study investigated the effects of TOR1 gene deletion on Saccharomyces cerevisiae through transcriptome analysis of wild-type and tor1Δ mutant cells during exponential development under non-stress circumstances. A significant number of differentially expressed genes (DEGs) were identified in the absence of TOR1, comprising 1665 upregulated genes and 1425 downregulated genes. These findings demonstrate the extensive impact of TOR signaling on several biological processes, including metabolism, stress response, and lifespan regulation. A significant number of differentially expressed genes (DEGs) were identified in the absence of TOR1, comprising 1665 upregulated genes and 1425 downregulated genes. These findings demonstrate the extensive impact of TOR signaling on several biological processes, including metabolism, stress response, and lifespan regulation. A total of 736 DEGs were associated with either replicative lifespan or chronological lifespan, further emphasizing the significance of TOR1 in aging. Although genes associated with glucose transporters and storage were upregulated, glycolytic genes remained unchanged, indicating a metabolic shift towards alternative pathways such as gluconeogenesis and the pentose phosphate pathway. Among these, HXK1 exhibited the highest upregulation in tor1Δ cells, contrasting with HXK2, whose expression remained stable. This suggests that HXK1, typically active under low glucose or caloric restriction, plays a crucial role in reregulating glucose metabolism in the absence of TOR1. The research also identified specific transcription factors, including ADR1, HAP4, and their paralogs, which were upregulated and bound only to the HXK1 promoter, pointing to their regulatory role in this metabolic shift. The findings indicate that TOR1 inactivation triggers nutrient- and energy-sensing mechanisms that redirect cellular resources towards stress adaptation and longevity, highlighting Tor1's crucial function in aging and proposing that modulation of the TOR pathway could be a potential strategy for anti-aging therapies.本研究通过对非应激条件下指数生长期的野生型与tor1Δ突变酿酒酵母（Saccharomyces cerevisiae）进行转录组分析，探究了TOR1基因敲除对酿酒酵母的影响。在TOR1缺失的情况下，研究共鉴定出大量差异表达基因（differentially expressed genes, DEGs），其中上调基因1665个，下调基因1425个。上述结果表明，TOR信号通路对代谢、应激响应及寿命调控等多种生物学过程具有广泛调控作用。在TOR1缺失的情况下，研究共鉴定出大量差异表达基因（differentially expressed genes, DEGs），其中上调基因1665个，下调基因1425个。上述结果表明，TOR信号通路对代谢、应激响应及寿命调控等多种生物学过程具有广泛调控作用。另有736个差异表达基因与复制寿命（replicative lifespan）或时序寿命（chronological lifespan）相关，进一步凸显了TOR1在衰老过程中的重要意义。尽管葡萄糖转运蛋白与储存相关基因出现上调，但糖酵解相关基因的表达未发生改变，这提示细胞代谢转向糖异生（gluconeogenesis）及磷酸戊糖途径（pentose phosphate pathway）等替代通路。其中，HXK1在tor1Δ细胞中呈现最高水平的上调，而HXK2的表达则保持稳定，这表明通常在低葡萄糖或热量限制（caloric restriction）条件下激活的HXK1，在TOR1缺失介导的葡萄糖代谢重调控中发挥关键作用。本研究还鉴定出ADR1、HAP4及其旁系同源物等特定转录因子（transcription factors），这些因子出现上调且仅结合HXK1启动子（promoter）区域，提示它们在该代谢转向过程中发挥调控功能。研究结果表明，TOR1失活会激活营养与能量感知机制，使细胞资源重新定向至应激适应与寿命延长过程，凸显了Tor1在衰老过程中的核心功能，并提出调控TOR通路或可成为抗衰老治疗（anti-aging therapies）的潜在策略。