{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:44:10Z","timestamp":1789865050699,"version":"4.0.1"},"reference-count":105,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSERC of Canada","award":["RGPIN 2014-04482"],"award-info":[{"award-number":["RGPIN 2014-04482"]}]},{"name":"Concordia University Chair Fund","award":["CC0113"],"award-info":[{"award-number":["CC0113"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms19030860","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T05:11:28Z","timestamp":1521090688000},"page":"860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Some Metabolites Act as Second Messengers in Yeast Chronological Aging"],"prefix":"10.3390","volume":"19","author":[{"given":"Karamat","family":"Mohammad","sequence":"first","affiliation":[{"name":"Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam\u00e9la","family":"Dakik","sequence":"additional","affiliation":[{"name":"Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younes","family":"Medkour","sequence":"additional","affiliation":[{"name":"Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lissa","family":"McAuley","sequence":"additional","affiliation":[{"name":"Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Mitrofanova","sequence":"additional","affiliation":[{"name":"Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5819-7545","authenticated-orcid":false,"given":"Vladimir","family":"Titorenko","sequence":"additional","affiliation":[{"name":"Department of Biology, Concordia University, 7141 Sherbrooke Street, West, SP Building, Room 501-13, Montreal, QC H4B 1R6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.1172539","article-title":"Extending healthy life span\u2014From yeast to humans","volume":"328","author":"Fontana","year":"2010","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cmet.2012.06.002","article-title":"Replicative and chronological aging in Saccharomyces cerevisiae","volume":"16","author":"Longo","year":"2012","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.15698\/mic2014.06.152","article-title":"Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae","volume":"1","author":"Leonov","year":"2014","journal-title":"Microb. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature08981","article-title":"Lessons on longevity from budding yeast","volume":"464","author":"Kaeberlein","year":"2010","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"V\u00e1chov\u00e1, L., C\u00e1p, M., and Palkov\u00e1, Z. (2012). Yeast colonies: A model for studies of aging, environmental adaptation, and longevity. Oxid. Med. Cell. Longev., 2012.","DOI":"10.1155\/2012\/601836"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/1574-6976.12060","article-title":"Budding yeast as a model organism to study the effects of age","volume":"38","author":"Julou","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.cellbio.23.090506.123509","article-title":"Replicative aging in yeast: The means to the end","volume":"24","author":"Steinkraus","year":"2008","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_8","first-page":"1209","article-title":"Measuring replicative life span in the budding yeast","volume":"28","author":"Steffen","year":"2009","journal-title":"J. Vis. Exp."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1101\/gr.074724.107","article-title":"Quantitative evidence for conserved longevity pathways between divergent eukaryotic species","volume":"18","author":"Smith","year":"2008","journal-title":"Genome Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ghavidel, A., Baxi, K., Ignatchenko, V., Prusinkiewicz, M., Arnason, T.G., Kislinger, T., Carvalho, C.E., and Harkness, T.A. (2015). A genome scale screen for mutants with delayed exit from mitosis: Ire1-independent induction of autophagy integrates ER homeostasis into mitotic lifespan. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005429"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.cmet.2015.09.008","article-title":"A comprehensive analysis of replicative lifespan in 4698 single-gene deletion strains uncovers conserved mechanisms of aging","volume":"22","author":"McCormick","year":"2015","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.15698\/mic2016.07.510","article-title":"Evidence for the hallmarks of human aging in replicatively aging yeast","volume":"3","author":"Janssens","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-59745-361-5_8","article-title":"The chronological life span of Saccharomyces cerevisiae","volume":"371","author":"Fabrizio","year":"2007","journal-title":"Methods Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-94-007-2561-4_5","article-title":"Chronological aging in Saccharomyces cerevisiae","volume":"57","author":"Longo","year":"2012","journal-title":"Subcell. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.4161\/cc.8.8.8287","article-title":"A molecular mechanism of chronological aging in yeast","volume":"8","author":"Burtner","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cell.2006.07.002","article-title":"Sirtuins in aging and age-related disease","volume":"126","author":"Longo","year":"2006","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.4161\/cc.21465","article-title":"pH neutralization protects against reduction in replicative lifespan following chronological aging in yeast","volume":"11","author":"Murakami","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.exger.2012.12.001","article-title":"Dietary restriction and mitochondrial function link replicative and chronological aging in Saccharomyces cerevisiae","volume":"48","author":"Delaney","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.bbrc.2015.03.085","article-title":"The longevity in the yeast Saccharomyces cerevisiae: A comparison of two approaches for assessment the lifespan","volume":"460","author":"Molon","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1146\/annurev-cellbio-092910-154010","article-title":"Driving the cell cycle through metabolism","volume":"28","author":"Cai","year":"2012","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1600-0854.2010.01144.x","article-title":"Peroxisome metabolism and cellular aging","volume":"12","author":"Titorenko","year":"2011","journal-title":"Traffic"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fphys.2012.00283","article-title":"Integration of peroxisomes into an endomembrane system that governs cellular aging","volume":"3","author":"Beach","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/iub.1183","article-title":"A network of interorganellar communications underlies cellular aging","volume":"65","author":"Leonov","year":"2013","journal-title":"IUBMB Life"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.bbalip.2013.08.006","article-title":"Sphingolipids and lifespan regulation","volume":"1841","author":"Huang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110","DOI":"10.15698\/mic2014.04.142","article-title":"Metabolites in aging and autophagy","volume":"1","author":"Schroeder","year":"2014","journal-title":"Microb. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cmet.2015.05.014","article-title":"Acetyl coenzyme A: A central metabolite and second messenger","volume":"21","author":"Pietrocola","year":"2015","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fgene.2016.00177","article-title":"Communications between mitochondria, the nucleus, vacuoles, peroxisomes, the endoplasmic reticulum, the plasma membrane, lipid droplets, and the cytosol during yeast chronological aging","volume":"7","author":"Dakik","year":"2016","journal-title":"Front. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tcb.2015.10.003","article-title":"TOR complexes and the maintenance of cellular homeostasis","volume":"26","author":"Eltschinger","year":"2016","journal-title":"Trends Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.plipres.2015.11.001","article-title":"Unraveling the role of the target of rapamycin signaling in sphingolipid metabolism","volume":"61","author":"Teixeira","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s41745-016-0013-1","article-title":"Conceptualizing eukaryotic metabolic sensing and signaling","volume":"97","author":"Laxman","year":"2017","journal-title":"J. Indian Inst. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00294-016-0617-z","article-title":"The slim, the fat, and the obese: Guess who lives the longest?","volume":"63","author":"Li","year":"2017","journal-title":"Curr. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.2741\/4638","article-title":"Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae","volume":"23","author":"Mitrofanova","year":"2018","journal-title":"Front. Biosci."},{"key":"ref_33","unstructured":"Fraenkel, D.G. (2011). Yeast Intermediary Metabolism, Cold Spring Harbor Laboratory Press."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1046\/j.1365-2958.2001.02283.x","article-title":"Role of the glutathione\/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions","volume":"39","author":"Grant","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00306","DOI":"10.7554\/eLife.00306","article-title":"Time line of redox events in aging postmitotic cells","volume":"2","author":"Brandes","year":"2013","journal-title":"Elife"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wei, M., Fabrizio, P., Madia, F., Hu, J., Ge, H., Li, L.M., and Longo, V.D. (2009). Tor1\/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000467"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.exger.2009.06.001","article-title":"Effect of calorie restriction on the metabolic history of chronologically aging yeast","volume":"44","author":"Goldberg","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1574-6976.2001.tb00574.x","article-title":"Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae","volume":"25","author":"Parrou","year":"2001","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.mad.2003.12.006","article-title":"Reserve carbohydrates maintain the viability of Saccharomyces cerevisiae cells during chronological aging","volume":"125","author":"Samokhvalov","year":"2004","journal-title":"Mech. Ageing Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.exger.2010.02.008","article-title":"Gene regulatory changes in yeast during life extension by nutrient limitation","volume":"45","author":"Wang","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3389\/fphys.2012.00256","article-title":"Caloric restriction extends yeast chronological lifespan by altering a pattern of age-related changes in trehalose concentration","volume":"3","author":"Kyryakov","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cmet.2012.05.013","article-title":"Mitochondrial respiratory thresholds regulate yeast chronological life span and its extension by caloric restriction","volume":"16","author":"Ocampo","year":"2012","journal-title":"Cell Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cao, L., Tang, Y., Quan, Z., Zhang, Z., Oliver, S.G., and Zhang, N. (2016). Chronological lifespan in yeast is dependent on the accumulation of storage carbohydrates mediated by Yak1, Mck1 and Rim15 kinases. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006458"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10522-015-9625-5","article-title":"Stratification of yeast cells during chronological aging by size points to the role of trehalose in cell vitality","volume":"17","author":"Svenkrtova","year":"2016","journal-title":"Biogerontology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69328","DOI":"10.18632\/oncotarget.20614","article-title":"Caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of a quiescent state, entry into a non-quiescent state and survival in the non-quiescent state","volume":"8","author":"Leonov","year":"2017","journal-title":"Oncotarget"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S1097-2765(00)80064-7","article-title":"Multiple effects of trehalose on protein folding in vitro and in vivo","volume":"1","author":"Singer","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/pro.3","article-title":"Effect of trehalose on protein structure","volume":"18","author":"Jain","year":"2009","journal-title":"Protein Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrm2240","article-title":"Hydrogen peroxide: A metabolic by-product or a common mediator of ageing signals?","volume":"8","author":"Giorgio","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1091\/mbc.12.2.323","article-title":"Remodeling of yeast genome expression in response to environmental changes","volume":"12","author":"Causton","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1126\/science.1059497","article-title":"Regulation of longevity and stress resistance by Sch9 in yeast","volume":"292","author":"Fabrizio","year":"2001","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.cmet.2013.04.003","article-title":"Epigenetic silencing mediates mitochondria stress-induced longevity","volume":"17","author":"Schroeder","year":"2013","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mad.2013.12.002","article-title":"Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan","volume":"135","author":"Schroeder","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6784","DOI":"10.1073\/pnas.102687599","article-title":"The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine","volume":"99","author":"Crespo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1101\/gad.1381406","article-title":"Extension of chronological life span in yeast by decreased TOR pathway signaling","volume":"20","author":"Powers","year":"2006","journal-title":"Genes Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/1574-6976.12065","article-title":"Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae","volume":"38","author":"Conrad","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/1567-1364.12097","article-title":"Molecular mechanisms linking the evolutionary conserved TORC1-Sch9 nutrient signalling branch to lifespan regulation in Saccharomyces cerevisiae","volume":"14","author":"Swinnen","year":"2014","journal-title":"FEMS Yeast Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.molcel.2007.04.020","article-title":"Sch9 is a major target of TORC1 in Saccharomyces cerevisiae","volume":"26","author":"Urban","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1101\/gad.532109","article-title":"Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis","volume":"23","author":"Huber","year":"2009","journal-title":"Genes Dev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12604","DOI":"10.1074\/jbc.C900020200","article-title":"Regulation of RNA polymerase III transcription involves SCH9-dependent and SCH9-independent branches of the target of rapamycin (TOR) pathway","volume":"284","author":"Lee","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.4161\/cc.8.24.10170","article-title":"Sch9 partially mediates TORC1 signaling to control ribosomal RNA synthesis","volume":"8","author":"Wei","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cmet.2007.02.009","article-title":"Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression","volume":"5","author":"Bonawitz","year":"2007","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"131","DOI":"10.18632\/aging.100016","article-title":"Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density","volume":"1","author":"Pan","year":"2009","journal-title":"Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/j.1365-2958.2004.04429.x","article-title":"PKA and Sch9 control a molecular switch important for the proper adaptation to nutrient availability","volume":"55","author":"Roosen","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2958.2008.06292.x","article-title":"Caffeine extends yeast lifespan by targeting TORC1","volume":"69","author":"Wanke","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00294-009-0287-1","article-title":"Life in the midst of scarcity: Adaptations to nutrient availability in Saccharomyces cerevisiae","volume":"56","author":"Smets","year":"2010","journal-title":"Curr. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Medvedik, O., Lamming, D.W., Kim, K.D., and Sinclair, D.A. (2007). MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae. PLoS Biol., 5.","DOI":"10.1371\/journal.pbio.0050261"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/j.1365-2958.2008.06450.x","article-title":"Yeast Yak1 kinase, a bridge between PKA and stress-responsive transcription factors, Hsf1 and Msn2\/Msn4","volume":"70","author":"Lee","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1534\/genetics.111.135731","article-title":"Nutritional control of growth and development in yeast","volume":"192","author":"Broach","year":"2012","journal-title":"Genetics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","article-title":"mTOR signaling in growth control and disease","volume":"149","author":"Laplante","year":"2012","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"944","DOI":"10.4161\/auto.28987","article-title":"ATG13: Just a companion, or an executor of the autophagic program?","volume":"10","author":"Alers","year":"2014","journal-title":"Autophagy"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.1091\/mbc.e07-05-0485","article-title":"Protein kinase A and Sch9 cooperatively regulate induction of autophagy in Saccharomyces cerevisiae","volume":"18","author":"Yorimitsu","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"17049","DOI":"10.1073\/pnas.0903316106","article-title":"The Tor and PKA signaling pathways independently target the Atg1\/Atg13 protein kinase complex to control autophagy","volume":"106","author":"Stephan","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"294","DOI":"10.4161\/auto.6.2.11129","article-title":"The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae","volume":"6","author":"Stephan","year":"2010","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Johnson, J.E., and Johnson, F.B. (2014). Methionine restriction activates the retrograde response and confers both stress tolerance and lifespan extension to yeast, mouse and human cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097729"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ruckenstuhl, C., Netzberger, C., Entfellner, I., Carmona-Gutierrez, D., Kickenweiz, T., Stekovic, S., Gleixner, C., Schmid, C., Klug, L., and Sorgo, A.G. (2014). Lifespan extension by methionine restriction requires autophagy-dependent vacuolar acidification. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004347"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Wu, Z., Song, L., Liu, S.Q., and Huang, D. (2013). Independent and additive effects of glutamic acid and methionine on yeast longevity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079319"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"160","DOI":"10.15698\/mic2014.05.147","article-title":"Autophagy extends lifespan via vacuolar acidification","volume":"1","author":"Ruckenstuhl","year":"2014","journal-title":"Microb. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"22679","DOI":"10.1074\/jbc.M502972200","article-title":"The sphingoid long chain base phytosphingosine activates AGC-type protein kinases in Saccharomyces cerevisiae including Ypk1, Ypk2, and Sch9","volume":"280","author":"Liu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1042\/BST0331170","article-title":"Signalling functions for sphingolipid long-chain bases in Saccharomyces cerevisiae","volume":"33","author":"Liu","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Huang, X., Liu, J., and Dickson, R.C. (2012). Down-regulating sphingolipid synthesis increases yeast lifespan. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002493"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1111\/acel.12107","article-title":"Reducing sphingolipid synthesis orchestrates global changes to extend yeast lifespan","volume":"12","author":"Liu","year":"2013","journal-title":"Aging Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/ncb1975","article-title":"Induction of autophagy by spermidine promotes longevity","volume":"11","author":"Eisenberg","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"961","DOI":"10.18632\/aging.100110","article-title":"Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol","volume":"1","author":"Morselli","year":"2009","journal-title":"Aging"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"716","DOI":"10.18632\/aging.100361","article-title":"Polyamines in aging and disease","volume":"3","author":"Minois","year":"2011","journal-title":"Aging"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cell.2014.11.048","article-title":"Endogenous hydrogen sulfide production is essential for dietary restriction benefits","volume":"160","author":"Hine","year":"2015","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/j.cell.2014.05.031","article-title":"The search for antiaging interventions: From elixirs to fasting regimens","volume":"157","author":"Bernier","year":"2014","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lee, C., and Longo, V. (2016). Dietary restriction with and without caloric restriction for healthy aging. F1000Res., 5.","DOI":"10.12688\/f1000research.7136.1"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.exger.2014.12.010","article-title":"Calorie restriction and methionine restriction in control of endogenous hydrogen sulfide production by the transsulfuration pathway","volume":"68","author":"Hine","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cell.2014.12.027","article-title":"A protein restriction-dependent sulfur code for longevity","volume":"160","author":"Shim","year":"2015","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.4161\/cc.8.14.8852","article-title":"Acetic acid effects on aging in budding yeast: Are they relevant to aging in higher eukaryotes?","volume":"8","author":"Burhans","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.4161\/cc.10.9.15464","article-title":"A genomic analysis of chronological longevity factors in budding yeast","volume":"10","author":"Burtner","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.4161\/cc.22042","article-title":"Acetic acid and acidification accelerate chronological and replicative aging in yeast","volume":"11","author":"Mirisola","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fmicb.2013.00033","article-title":"Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid","volume":"4","author":"Giannattasio","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1007\/s00018-016-2197-y","article-title":"External and internal triggers of cell death in yeast","volume":"73","author":"Falcone","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.cmet.2014.02.010","article-title":"Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme A stimulates autophagy and prolongs lifespan","volume":"19","author":"Eisenberg","year":"2014","journal-title":"Cell Metab."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.molcel.2014.01.016","article-title":"Regulation of autophagy by cytosolic acetyl-coenzyme A","volume":"53","author":"Pietrocola","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.cell.2005.08.042","article-title":"Sir2 blocks extreme life-span extension","volume":"123","author":"Fabrizio","year":"2005","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3707","DOI":"10.4161\/15384101.2014.965003","article-title":"Mechanism of liponecrosis, a distinct mode of programmed cell death","volume":"13","author":"Richard","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4161\/cc.26885","article-title":"Macromitophagy, neutral lipids synthesis, and peroxisomal fatty acid oxidation protect yeast from \u201cliponecrosis\u201d, a previously unknown form of programmed cell death","volume":"13","author":"Sheibani","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Mohammad, K., Dakik, P., Medkour, Y., McAuley, M., Mitrofanova, D., and Titorenko, V.I. (2018). Yeast cells exposed to exogenous palmitoleic acid either adapt to stress and survive or commit to regulated liponecrosis and die. Oxid. Med. Cell. Longev., 2018.","DOI":"10.1155\/2018\/3074769"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.4161\/cc.10.18.16947","article-title":"In search of housekeeping pathways that regulate longevity","volume":"10","author":"Beach","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/bs.ircmb.2015.09.003","article-title":"Cell-nonautonomous mechanisms underlying cellular and organismal aging","volume":"321","author":"Medkour","year":"2016","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.4161\/cc.21754","article-title":"Lithocholic acid extends longevity of chronologically aging yeast only if added at certain critical periods of their lifespan","volume":"11","author":"Burstein","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_104","unstructured":"Cantley, L., Hunter, T., Sever, R., and Thorner, J. (2014). Signal Transduction: Principles, Pathways, and Processes, Cold Spring Harbor Laboratory Press."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Lim, W., Mayer, B., and Pawson, T. (2015). Cell Signaling: Principles and Mechanisms, Garland Science.","DOI":"10.1201\/9780429258893"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/3\/860\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:07Z","timestamp":1760194627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/3\/860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":105,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["ijms19030860"],"URL":"https:\/\/doi.org\/10.3390\/ijms19030860","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,15]]}}}