We assessed the chronological lifespans of yeast deleted for genes

As mentioned above, a recent study has demonstrated that dietary Meth-R robustly extends yeast chronological lifespan. Our aim, however, was to develop cell-based model systems wherein the methionine-restricted state is produced by genetic means, which has the benefit of allowing all aging experiments to be performed using a single media preparation. Although the intent in preparing matched normal and methionine-limited media is to hold the concentrations of all other components constant, in practice, small differences between media preparations may somewhat confound interpretation of studies utilizing dietary Meth-R. To test whether genetic interventions that abrogate methionine biosynthesis extend Benztropine mesylate lifespan in yeast, we assessed the chronological lifespans of yeast deleted for either of two genes involved in methionine Triclabendazole production. We found these mutants to be significantly longer-lived than wild-type. To determine the extent to which this intervention recapitulates dietary Meth-R in our strain background, we measured the survival of wild-type haploid yeast cells aged in either normal media or media lacking both methionine and cysteine, the latter of which can be converted into methionine via a salvage pathway. While we found that Meth-R in yeast recapitulated the benefits of this manipulation to rodents, it was unclear whether the benefit to yeast was due to methionine limitation, specifically, or merely the consequence of reducing the cellular pool of any single amino acid. It was previously demonstrated that limitation of total amino acids extends yeast chronological lifespan, and a subsequent study revealed that removal of either asparagine or glutamate from culture media results in a moderate extension of median lifespan. The latter finding, however, is difficult to reconcile with data from another group indicating that cells aged in media containing 20-fold higher levels of glutamate than normal are also long-lived. What is clear, however, is that amino acid availability can have profound consequences for the stationary phase survival of yeast.

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