Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
Department of New Biology, DGIST, Daegu, 42988, Republic of Korea.
Adv Biol (Weinh). 2024 Sep;8(9):e2400083. doi: 10.1002/adbi.202400083. Epub 2024 May 8.
The regulation of complex energy metabolism is intricately linked to cellular energy demands. Caloric restriction (CR) plays a pivotal role in modulating the expression of genes associated with key metabolic pathways, including glycolysis, the tricarboxylic acid (TCA) cycle, and the glyoxylate cycle. In this study, the chronological lifespan (CLS) of 35 viable single-gene deletion mutants under both non-restricted and CR conditions, focusing on genes related to these metabolic pathways is evaluated. CR is found to increase CLS predominantly in mutants associated with the glycolysis and TCA cycle. However, this beneficial effect of CR is not observed in mutants of the glyoxylate cycle, particularly those lacking genes for critical enzymes like isocitrate lyase 1 (icl1Δ) and malate synthase 1 (mls1Δ). This analysis revealed an increase in isocitrate lyase activity, a key enzyme of the glyoxylate cycle, under CR, unlike the activity of isocitrate dehydrogenase, which remains unchanged and is specific to the TCA cycle. Interestingly, rapamycin, a compound known for extending lifespan, does not increase the activity of the glyoxylate cycle enzyme. This suggests that CR affects lifespan through a distinct metabolic mechanism.
复杂的能量代谢调节与细胞能量需求密切相关。热量限制（CR）在调节与关键代谢途径相关的基因表达方面起着关键作用，包括糖酵解、三羧酸（TCA）循环和乙醛酸循环。在这项研究中，评估了非限制和 CR 条件下 35 种可行的单基因缺失突变体的时序寿命（CLS），重点关注与这些代谢途径相关的基因。CR 主要增加了与糖酵解和 TCA 循环相关的突变体的 CLS。然而，CR 的这种有益效果在乙醛酸循环的突变体中没有观察到，特别是那些缺乏关键酶如异柠檬酸裂合酶 1（icl1Δ）和苹果酸合酶 1（mls1Δ）的突变体。这项分析表明，CR 会增加乙醛酸循环中关键酶异柠檬酸裂合酶的活性，而不是 TCA 循环中异柠檬酸脱氢酶的活性，后者保持不变。有趣的是，雷帕霉素，一种已知能延长寿命的化合物，不会增加乙醛酸循环酶的活性。这表明 CR 通过一种独特的代谢机制影响寿命。
