CONICET | Buscador de Institutos y Recursos Humanos

Lifespan extension has been a human challenge since ever. Aging is a multifactorial and complex process characterized by a progressive damage of cellular functions that inevitably leads to death. It is regulated by numerous nutrient-sensing pathways. Amino acids levels are sensed by at least two evolutionarily conserved and intersecting mechanisms: one involving Gcn2 kinase and the other involving the TORC1 kinase. Dietary 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 aim of this work was to study how an excess of amino acids affect longevity in prototrophic yeast cells and to determine which nutrient-pathways are involved. 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. We used wild type cells and cells deficient in the kinase Tor1 and in the transcription factor, Gcn4, a key regulator of amino acid biosynthesis and the main target of the kinase Gcn2. Longevity was affected neither by growth conditions nor by mutant genotypes assayed. When tolerance against thermal stress was analysed during the aging process, we found that cells lacking GCN4 were less resistant to thermal stress than the other strains used and that amino acids had a protective effect; however, no differences during aging were observed when cells were subjected to oxidative stress. Also, we determined stress tolerance, autophagy and the activity of the unfolded protein response (UPR) pathway in cells at the exponential and stationary growth phases. Differences found before aging started did not explain the similar CLS behaviour observed. Altogether these results allow us to conclude that lifespan extension does not result solely from increased stress resistance, UPR or autophagy activation, supporting the idea of the complexity of the aging process.