Ammonium is a key determinant on the dietary restriction of yeast chronological aging in culture medium

// Júlia Santos 1,2 , Fernanda Leitão-Correia 3 , Maria João Sousa 3,* and Cecília Leão 1,2,* 1 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal 2 ICVS/3B’s - PT Government Associate Laboratory, Braga, Guimarães, Portugal 3 Molecular and Environmental Biology Centre (CBMA), Department of Biology, University of Minho, Braga, Portugal * These authors contributed equally to this work Correspondence: Maria João Sousa, email: // Keywords : Ammonium, lifespan, dietary restriction, amino acid restriction, yeast Received : October 16, 2014 Accepted : December 02, 2014 Published : December 03, 2014 Abstract New evidences have recently emerged from studies in yeast and in higher eukaryotes showing the importance of nutrient balance in dietary regimes and its effects on longevity regulation.We have previously shown that manipulation ofammoniumconcentration in the culture and/or aging medium can drastically affect chronological lifespan (CLS)of Saccharomyces cerevisiae , especially in amino acid restricted cells. Here we describe that the CLS shortening under amino acid restriction can be completely reverted by removing ammonium from the culture medium. Furthermore, the absence of ammonium, and of any rich nitrogen source, was so effective in extending CLS that no beneficial effect could be observed by further imposing calorie restriction conditions. When present in the culture medium,ammoniumimpaired the consumption of theauxotrophy-complementing amino acidsand caused in an improper cell cycle arrest of the culture. TOR1 deletion reverted ammonium effects both in amino acid restricted and non-restricted cultures, whereas, Ras2p and Sch9p seem to have only a milder effect in the mediation ofammonium toxicity under amino acid restriction and no effect on non-restricted cultures.Our studies highlight ammonium as a key effector in the nutritional equilibrium between rich and essential nitrogen sources and glucose required for longevity promotion.