Some Metabolites Act as Second Messengers in Yeast Chronological Aging

Abstract

The concentrations of some key metabolic intermediates play essential roles in regulating the longevity of the chronologically aging yeast Saccharomyces cerevisiae. These key metabolites are detected by certain ligand-specific protein sensors that respond to concentration changes of the key metabolites by altering the efficiencies of longevity-defining cellular processes. The concentrations of the key metabolites that affect yeast chronological aging are controlled spatially and temporally. Here, we analyze mechanisms through which the spatiotemporal dynamics of changes in the concentrations of the key metabolites influence yeast chronological lifespan. Our analysis indicates that a distinct set of metabolites can act as second messengers that define the pace of yeast chronological aging. Molecules that can operate both as intermediates of yeast metabolism and as second messengers of yeast chronological aging include reduced nicotinamide adenine dinucleotide phosphate (NADPH), glycerol, trehalose, hydrogen peroxide, amino acids, sphingolipids, spermidine, hydrogen sulfide, acetic acid, ethanol, free fatty acids, and diacylglycerol. We discuss several properties that these second messengers of yeast chronological aging have in common with second messengers of signal transduction. We outline how these second messengers of yeast chronological aging elicit changes in cell functionality and viability in response to changes in the nutrient, energy, stress, and proliferation status of the cell.

The cell biology of quiescent yeast – a diversity of individual scenarios

“…The purpose of the present Review is to scrutinize S. cerevisiae quiescence with the eyes of a cell biologist in the context of carbon exhaustion. Many excellent reviews have focused on genes and signaling cascades that link nutrients to quiescence establishment in S. cerevisiae (Fabrizio and Longo, 2003;De Virgilio, 2012;Mohammad et al, 2018;Gray et al, 2004;Herman, 2002;Zaman et al, 2008;Broach, 2012) and these aspects will thus not be discussed. Here, we will illustrate that the properties of quiescent cells vary depending on the individuals and evolve with time, thereby challenging once more the preconceived idea of quiescence uniformity.…”

The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae

“…Exhibits either an anti-aging or pro-aging effect Leonov et al ( 2017 ), Ocampo et al ( 2012 ) Amino acids Regulates longevity-defining programs via downstream activation of Target of Rapamycin complex 1 (TORC1) and proteins (Sch9, Atg13, Tap42) Nutrient-sensing protein kinase A (PKA), Activation of protein kinase activity of the TORC1 Intermediates in the yeast cell mitochondria and in the TCA cycle Pro-aging molecule which function by phosphorylating downstream protein targets (Sch9, Atg13, Tap42) Swinnen et al ( 2014 ) Ethanol Anaplerotic conversion of acetyl CoA to citrate and acetyl carnitine. Catabolize peroxisomal β-oxidation of fatty acids to acetyl-CoA Accelerate CLS by increasing age-related mode of regulated cell death (RCD) i.e., liponecrosis Pro-aging of sirtuin deacetylase (Sir2) occur by inhibiting Adh2-driven conversion of ethanol to acetaldehyde Mitochondrial and cytosol Accelerates yeast chronological aging Mohammad et al ( 2018 ) Free fatty acid (FFA) and diacylglycerol (DAG) Accelerate the onset of age-related liponecrotic RCD Ethanol-dependent suppression of peroxisomal β-oxidation pathway Accumulation of unoxidized FFA in peroxisomes elicits negative-feedback (buildup of FFA and DAG) ER and lipid droplets FFA and DAG serve as pro-aging metabolites shortened yeast CLS Beach and Titorenko ( 2011 ) Hydrogen sulfide (H 2 S) Endogenously synthesize in the transsulfuration (TSP) pathway from methionine to cysteine Water and fat-soluble gas produce by assimilation of inorganic sulfate Promote electron transport chain in mitochondria and activate transcription of stress-response genes Mitochondrial electron transport chain It release in culture triggers yeast CLS. It also inhibit yeast chronological aging by CR Hine et al ( 2015 ) …”

“…Interestingly, there is interplay between aging progression and secretion of secondary metabolites. These metabolites modulate the rate of aging, and may include sphingolipids (Ren and Hannun 2016 ), NADPH (Mohammad et al 2020 ), hydrogen peroxide (Dakik and Titorenko et al 2016 ), ethanol (Mohammad et al 2018 ), acetic acid (Baroni et al 2020 ), and hydrogen sulfide (Huang et al 2017 ), among others.…”

Yeast Life Span and its Impact on Food Fermentations

“…Glycerol, however, plays a beneficial role in the CLS [16]. Its production lowers metabolite flow from glucose fermentation into ethanol and acetic acid, causing also the increase of the concentration of NAD + (a sirtuin activator, see below) [17].…”