Abstract
It has been found that calorie restriction (CR) can extend the average and maximum life span from yeast to primates and delay the onset of age‐associated pathologies. Mismatch repair and double strand break repair systems are major DNA repair pathways whose function are critical for maintaining genome stability. The inactivation of these systems in human pathway has been reported to cause cancer predisposition such as Hereditary Nonpolyposis Colorectal Cancer, Werner and Bloom syndromes. By using Saccharomyces cerevisiae model system for CR and aging studies, DNA repair defective cells (msh2Δ, msh3Δ, msh6Δ and sgs1Δ) were cultured with normal (2% glucose) and CR (0.5% glucose) medium. Genome stability studies were analyzed by CANr, Homr and Lysr mutation assay. Results show that CR can significantly extend the lifespan of all wild‐type and mutants. Besides, CR shows significant decrease in HOMr mutation frequency by 2.7 × 104‐fold in msh2Δ mutant, whereas by 2.4 × 106‐fold and 1.4 × 106‐fold reduction in msh3Δ mutant for HOMr and LYSr assay respectively. In addition, for sgs1Δ mutant, there are significant decreases in HOMr and LYSr assay by two‐fold. Under normal condition, msh2Δ, msh3Δ and sgs1Δ cells found to have regrow phenotype upon aging. However, this phenotype was diminished under CR condition. Thus, CR promotes genome stability in DNA repair defective cells especially in msh2Δ, msh3Δ and sgs1Δ mutants.
Published Version
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