Nutrimental determinants of chronological aging and competitiveness in the snf1Δ Warburg model

Abstract

Cancer, one of the worlds leading causes of death, is characterized by a complex metabolic reprogramming that features the Warburg effect as one of its hallmarks. The Warburg effect involves increased glucose and amino acid metabolism, which promotes tumor proliferation and progression. Although cancer has historically been attributed to genetic mutations, recent studies suggest a possible metabolic origin. However, a key characteristic of cancer cells is their greater adaptability than normal cells, as evidenced by their resistance to chemotherapy, which stems from their high mutability. This underscores the need to examine the relationship between metabolic reprogramming and cancer development from both metabolic and evolutionary perspectives. In this context, Saccharomyces cerevisiae snf1{Delta} strain has emerged as an ideal cellular model for studying the Warburg effect. This study aimed to determine whether deletion of the SNF1 gene in S. cerevisiae affects its chronological aging and competitiveness in a glucose and amino acid-dependent manner. Herein, we provide evidence that the snf1{Delta} strain changes the chronological aging depending on nutrimental condition, under low-nutrient levels shortens (0.1% glucose + 0.1x amino acids), and increases under high-nutrient levels (5% glucose + 3x amino acids). Competitiveness of the snf1{Delta} strain in co-cultivation with wild-type was also improved in 5% glucose + 3x amino acids, by approximately 2 Log10. These results indicate that snf1{Delta} strain aging and competitiveness are also sensitive to nutrimental status, as was observed in cancer cells.