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.
Highlights
Studies of the budding yeast Saccharomyces cerevisiae have led to the discovery of genes, signaling pathways, and small molecules that define the rate of cellular aging in this unicellular eukaryote [1,2,3]
Based on the important advance in our understanding of these mechanisms, we conclude that a distinct group of metabolites act as second messengers that define the pace of yeast chronological aging
It is noteworthy that some of those metabolites that cannot act as low molecular weight transmissible longevity factors may change metabolism within the “host” cell so that this cell may respond by altering the production of acetic acid and/or other metabolites that can act via both cell-autonomous and cell-non-autonomous mechanisms
Summary
Studies of the budding yeast Saccharomyces cerevisiae have led to the discovery of genes, signaling pathways, and small molecules that define the rate of cellular aging in this unicellular eukaryote [1,2,3]. Recent studies have demonstrated that the intracellular and extracellular concentrations of some key metabolites play essential roles in regulating the longevity of chronologically aging S. cerevisiae [2,3,4,5,15,16,20,21,22,23,24,25,26,27,28,29,30,31,32]. NADPH has a specific role in longevity assurance of chronologically aging yeast because it provides electrons for thioredoxin and glutathione reductase systems (TRR and GTR, respectively) [34,35] Both these NADPH-dependent reductase systems play essential roles in the maintenance of intracellular redox homeostasis, thereby decreasing the extent of oxidative damage to thiol-containing proteins that reside in the cytosol, nucleus, and mitochondria of yeast cells [34,35]. Iitsispprerseesnentltylyuunnkknnoowwnn iiff tthhiiss sseeccoonnddmmecehcahnainsmisminvionlvvoelsvseosmseopmroetepinrosteenisnorssetnhsaotrrsespthoantd rtoesapnoinndcretaoseainn gilnyccreeraoslecoinncengtlryacteioronl bcyonsctiemnutrlaattiionng cbeyrtsatiinmsutrleastisnrgescpeorntasienpsrtorceessssreessipnoynesaestpcreolclse.sTsehsiridnmyeeachstanceislmls.: Tanhiirndcrmeaescehianngislumc:oasen fienrcmreeansteaitniognlutocogsleycfeerrmoleanltloatwiosnatnoignlcyrceearsoel ianllboowtshatnheinincrteraacseelilnulbaortchotnhceeninttrraatcioenlluolfaNr cAoDnc+enantrdattihoen ionftrNacAeDllu+ laanrdNtAheDi+n/tNraAceDllHularartNioA, tDhe+/rNebAyDseHttirnagtiou,pthaeprerob-ylosnegtteivnigtyucpelaluplraor-ploanttgeervniitny cchelrlounlaorlopgaicttaelrlyn aingicnhgroSn. coelroegviicsiaalely(Faiggiunrge S1.Bc)e[r3ev,3i6si]a.e (Figure 1B) [3,36]
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