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Nitrogen and carbon source balance determines longevity, independently of fermentative or respiratory metabolism in the yeast Saccharomyces cerevisiae

2016; Impact Journals LLC; Volume: 7; Issue: 17 Linguagem: Inglês

10.18632/oncotarget.8656

1949-2553

Júlia Santos, Fernanda Leitão-Correia, Maria João Sousa, Cecı́lia Leão,

Muscle Physiology and Disorders

// 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 have contributed equally to this work Correspondence to: Maria João Sousa, email: // Keywords : nitrogen source, prototrophic yeast, chronological life span, aging, Saccharomyces cerevisiae, Gerotarget Received : September 25, 2015 Accepted : March 28, 2016 Published : April 08, 2016 Abstract Dietary regimens have proven to delay aging and age-associated diseases in several eukaryotic model organisms but the input of nutritional balance to longevity regulation is still poorly understood. Here, we present data on the role of single carbon and nitrogen sources and their interplay in yeast longevity. Data demonstrate that ammonium, a rich nitrogen source, decreases chronological life span (CLS) of the prototrophic Saccharomyces cerevisiae strain PYCC 4072 in a concentration-dependent manner and, accordingly, that CLS can be extended through ammonium restriction, even in conditions of initial glucose abundance. We further show that CLS extension depends on initial ammonium and glucose concentrations in the growth medium, as long as other nutrients are not limiting. Glutamine, another rich nitrogen source, induced CLS shortening similarly to ammonium, but this effect was not observed with the poor nitrogen source urea. Ammonium decreased yeast CLS independently of the metabolic process activated during aging, either respiration or fermentation, and induced replication stress inhibiting a proper cell cycle arrest in G0/G1 phase. The present results shade new light on the nutritional equilibrium as a key factor on cell longevity and may contribute for the definition of interventions to promote life span and healthy aging.