AMINO ACIDS-SENSITIVE PATHWAYS DIFFERENTIALLY AFFECT LIFESPAN IN YEASTS

VALENCIA-GUILLEN JENNIFFER; CORREA-GARCÍA, SUSANA RAQUEL; MUÑOZ SEBASTIAN ANIBAL; BERMÚDEZ-MORETTI, MARIANA; GULIAS JUAN FACUNDO; BIRENBAUM, JOAQUÍN

Paraná

Congreso; LIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2018

SAIB

Dietary regimens have proven to promote longevity in several eukaryotic model organisms including the budding yeast Saccharomycescerevisiae. These interventions are effective strategies for preventing aging and diseases and many of them are linked to amino acid and proteinlevels. The internalization of amino acids is mediated by the Ssy1?Ptr3?Ssy5 (SPS) sensing pathway, their assimilation is regulated in the NCRsupra?pathway by the TORC1 kinase, and during amino acid starvation the GAAC pathway is activated. The aim of this work was to study howthese amino acid?sensitive pathways affect lifespan. We used wild type cells and cells deficient in genes participating in these metabolicpathways. Chronological lifespan (CLS) was measured using the colony forming unit spot assay in cells grown in the absence and in the presenceof all amino acids. Lifespan decreases in wild type cells grown with amino acids and in cells deficient in genes of the GAAC pathway; whereasthe TOR1 deficiency extends longevity. When tolerance against thermal stress was analysed during the aging process, we found that cells lackingLeu3, a transcription factor involved in the GAAC pathway, are less resistant and cells lacking Tor1 and Gln3 are more resistant than the otherstrains used. The amino acid presence has a protective effect in all cases assayed. We also determined that the SPS and GAAC pathwaysparticipate in both autophagy and the unfolded protein response (UPR) pathways. Altogether these results allow us to conclude that the pathwaysmodulated by amino acids regulate lifespan and other age?associated processes in opposite ways.