Mannarino Sérgio C, Amorim Maria A, Pereira Marcos D, Moradas-Ferreira Pedro, Panek Anita D, Costa Vítor, Eleutherio Elis C A
Departamento de Bioquímica, Instituto de Química, UFRJ, 21941-909 Rio de Janeiro, RJ, Brazil.
Mech Ageing Dev. 2008 Dec;129(12):700-5. doi: 10.1016/j.mad.2008.09.001. Epub 2008 Sep 18.
Calorie restriction increases longevity of mammals and yeasts but this mechanism remains unclear. In this study, the role of glutathione on lifespan extension induced by calorie restriction was investigated by using a Saccharomyces cerevisiae strain deficient in glutathione synthesis (gsh1). We observed an increase in chronological lifespan of calorie-restricted gsh1 mutant cells, compared to WT (wild type) strain, which was associated with a reduction in the levels of oxidative stress biomarkers. The gsh1 strain showed an increase in cell yield under calorie restriction that was associated with a higher pyruvate kinase activity and a reduction in oxygen consumption and aconitase activity. This indicates that the respiratory metabolism is decreased in gsh1 mutant cells. The lifespan extension of gsh1 mutant cells did not represent an advantage at long term, since old cells of gsh1 strain showed a higher frequency of petite mutants. In addition, aged WT cells outlast aged gsh1 mutant cells in direct competition assays in a fresh medium. These results suggest that glutathione is required for the beneficial effects of calorie restriction on cellular longevity.
热量限制可延长哺乳动物和酵母的寿命，但这种机制仍不清楚。在本研究中，通过使用缺乏谷胱甘肽合成的酿酒酵母菌株（gsh1），研究了谷胱甘肽在热量限制诱导的寿命延长中的作用。我们观察到，与野生型（WT）菌株相比，热量限制的gsh1突变细胞的时序寿命增加，这与氧化应激生物标志物水平的降低有关。gsh1菌株在热量限制下细胞产量增加，这与较高的丙酮酸激酶活性以及氧气消耗和乌头酸酶活性的降低有关。这表明gsh1突变细胞的呼吸代谢降低。gsh1突变细胞的寿命延长从长期来看并不具有优势，因为gsh1菌株的老龄细胞显示出较高频率的小菌落突变体。此外，在新鲜培养基的直接竞争试验中，老龄野生型细胞比老龄gsh1突变细胞存活时间更长。这些结果表明，谷胱甘肽是热量限制对细胞寿命产生有益影响所必需的。
