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.
Highlights
Longevity regulation in yeast and in higher eukaryotes involves several regulatory mechanisms from nutrient-signaling pathways and autophagy to metabolic shifts in energy-generating processes [1,2,3,4,5,6,7]
A rich nitrogen source, decreases chronological life span (CLS) of the prototrophic Saccharomyces cerevisiae strain PYCC 4072 in a concentrationdependent manner and, that CLS can be extended through ammonium restriction, even in conditions of initial glucose abundance
An association of mitochondrial respiration with glucose aging signaling has been described showing that the chronological life span (CLS) of respiratory-deficient strains with a respiratory capacity above the critical threshold during growth is extended by Caloric restriction (CR) to wild-type strains [8]
Summary
Longevity regulation in yeast and in higher eukaryotes involves several regulatory mechanisms from nutrient-signaling pathways and autophagy to metabolic shifts in energy-generating processes [1,2,3,4,5,6,7]. Several of the major conserved pro-aging pathways have been extensively studied in yeast, with multiple studies in this eukaryotic model unraveling the relation between longevity, nutrients and metabolic shifts that regulate survival [8,9,10,11]. This study presented evidence that the extended CLS encountered in CR cells can be achieved in non-CR cells by increasing respiratory capacity during growth only if accompanied by enhancement of cell stress resistance mechanisms that promote survival in stationary phase such as accumulation and mobilization of nutrient storage. Others have reported metabolic changes in the Target Of Rapamycin- ortholog of the mammalian S6 kinase (TOR-SCH9) signaling inhibition that lead to acetic acid catabolism and to trehalose accumulation and longevity promotion [18]
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