AMINO ACID METABOLISM AFFECTS CHRONOLOGICAL LIFESPAN IN PROTOTROPHIC YEASTS

JOAQUÍN MANUEL BIRENBAUM; MARIANA BERMÚDEZ-MORETTI; SEBASTIAN ANÍBAL MUÑOZ; SUSANA CORREA-GARCÍA; JUAN FACUNDO GULÍAS; JENNIFFER VALENCIA GUILLEN

Paraná

Congreso; LIV REUNION ANUAL SOCIEDAD ARGENTINA DE INVESTIGACION EN BIOQUIMICA Y BIOLOGIA MOLECULAR; 2018

SOCIEDAD ARGENTINA DE INVESTIGACIÓN BIOQUÍMICA Y BIOLOGÍA MOLECULAR-SAIB

Dietary regimens have proven to promote longevity in several eukaryotic model organisms including the budding yeast Saccharomyces cerevisiae. These interventions are effective strategies for preventing aging and diseases and many of them are linked to amino acid and protein levels and their regulation. The internalization of amino acids is mediated by the Ssy1-Ptr3-Ssy5 (SPS) sensing pathway, then their assimilation is regulated in the NCR supra-pathway by the TORC1 kinase, and during amino acid starvation the GAAC pathway is activated. The aim of this work was to study how these amino acid-sensitive pathways affect lifespan. We used wild type cells and cells deficient genes participating in these vias. Chronological lifespan (CLS) was measured using the colony forming unit spot assay in cells grown in the absence and in the presence of all amino acids. Lifespan decreases in cells deficient in genes of the GAAC pathway, whereas the TOR1 deficiency prolongs it. When tolerance against thermal stress was analysed during the aging process, we found that cells lacking LEU3, a transcription factor involved in the GAAC pathway, are less resistant and cells lacking TOR1 and GLN3 are more resistant than the other strains used and that amino acid presence have a protective effect. Also, we determined that the SPS and GAAC pathways participate in both autophagy and the unfolded protein response (UPR) pathways, two lifespan-related processes. Altogether these results allow us to conclude that amino acids and the pathways they modulate regulate lifespan in opposite way