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Aging and the Survival of Quiescent and Non-quiescent Cells in Yeast Stationary-Phase Cultures

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Aging Research in Yeast

Part of the book series: Subcellular Biochemistry ((SCBI,volume 57))

Abstract

In this chapter, we argue that with careful attention to cell types in stationary-phase cultures of the yeast, S. cerevisiae provide an excellent model system for aging studies and hold much promise in pinpointing the set of causal genes and mechanisms driving aging. Importantly, a more detailed understanding of aging in this single celled organism will also shed light on aging in tissue-complex model organisms such as C. elegans and D. melanogaster. We feel strongly that the relationship between aging in yeast and tissue-complex organisms has been obscured by failure to notice the heterogeneity of stationary-phase cultures and the processes by which distinct cell types arise in these cultures. Although several studies have used yeast stationary-phase cultures for chronological aging, the majority of these studies have assumed that cultures in stationary phase are homogeneously composed of a single cell type. However, genome-scale analyses of yeast stationary-phase cultures have identified two major cell fractions: quiescent and non-quiescent, which we discuss in detail in this chapter. We review evidence that cell populations isolated from these cultures exhibit population-specific phenotypes spanning a range of metabolic and physiological processes including reproductive capacity, apoptosis, differences in metabolic activities, genetic hyper-mutability, and stress responses. The identification, in S. cerevisiae, of multiple sub-populations having differentiated physiological attributes relevant to aging offers an unprecedented opportunity. This opportunity to deeply understand yeast cellular (and population) aging programs will, also, give insight into genomic and metabolic processes in tissue-complex organism, as well as stem cell biology and the origins of differentiation.

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Notes

  1. 1.

    Please note that I have been as guilty as any in the misuse of the terms “inviability” and “survival”, dating back to the years when I studied the HSP70 genes (Werner-Washburne et al. 1987).

  2. 2.

    It is also important, as senior scientists, that we communicate this to our students: (1) so they make a mental note to check methods every time they read “survival”, “death”, or “inviability” and (2) as a commitment to improving scientific discourse.

References

  • Aerts AM, Zabrocki P, Govaert G, Mathys J, Carmona-Gutierrez D, Madeo F et al (2009) Mitochondrial dysfunction leads to reduced chronological lifespan and increased apoptosis in yeast. FEBS Lett 583(1):113–117

    Article  PubMed  CAS  Google Scholar 

  • Allen C, Buttner S, Aragon AD, Thomas J, Meirelles O, Jaetao J et al (2006) Isolation of quiescent and non-quiescent cells from stationary-phase yeast cultures. J Cell Biol 174:89–100

    Article  PubMed  CAS  Google Scholar 

  • Amitai S, Kolodkin-Gal I, Hananya-Meltabashi M, Sacher A, Engelberg-Kulka H (2009) Escherichia coli MazF leads to the simultaneous selective synthesis of both death proteins and survival proteins. PLoS Genet 5(3):e1000390

    Article  PubMed  Google Scholar 

  • Aragon AD, Quiñones GA, Thomas EV, Roy S, Werner-Washburne M (2006) Release of extraction-resistant mRNA in stationary-phase S. cerevisiae produces a massive increase in transcript abundance in response to stress. Genome Biol 7:R9. doi:10.1186/gb-2006-1187-1182-r1189

    Article  PubMed  Google Scholar 

  • Aragon AD, Rodriguez AL, Meirelles O, Roy S, Davidson GS, Tapia PH et al (2008) Characterization of differentiated quiescent and nonquiescent cells in yeast stationary-phase cultures. Mol Biol Cell 19(3):1271–1280

    Article  PubMed  CAS  Google Scholar 

  • Ashrafi K, Sinclair D, Gordon JI, Guarente L (1999) Passage through stationary phase advances replicative aging in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 96:9100–9105

    Article  PubMed  CAS  Google Scholar 

  • Bartke A (2008) Insulin and aging. Cell Cycle 7(21):3338–3343

    Article  PubMed  CAS  Google Scholar 

  • Bitterman K, Medvedik O, Sinclair D (2003) Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin. Microbiol Mol Biol Rev 67(3):376–399

    Article  PubMed  CAS  Google Scholar 

  • Breitenbach M, Laun P, Heeren G, Jarolim S, Frohlich K-U, Wissing S, Pichova A (2003) Yeast as a model for ageing and apoptosis research. In: Nyström T, Osiewacz HD (eds) Topics in current genetics, vol 3. Model systems in aging. Springer, Berlin and Heidelberg, pp 61–97

    Google Scholar 

  • Burtner CR, Murakami CJ, Kennedy BK, Kaeberlein M (2009) A molecular mechanism of chronological aging in yeast. Cell Cycle 8(8):1256–1270

    Article  PubMed  CAS  Google Scholar 

  • Buttner S, Bitto A, Ring J, Augsten M, Zabrocki P, Eisenberg T et al (2008) Functional mitochondria are required for alpha-synuclein toxicity in aging yeast. J Biol Chem 283(12):7554–7560

    Article  PubMed  Google Scholar 

  • Buttner S, Eisenberg T, Herker E, Carmona-Gutierrez D, Kraemer G, Madeo F (2006) Why yeast cells can undergo apoptosis: death in times of peace, love, and war. J Cell Biol 175(4):521–525

    Article  PubMed  Google Scholar 

  • Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120(4):513–522

    Article  PubMed  CAS  Google Scholar 

  • Campisi J, di Fagagna FD (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8(9):729–740

    Article  PubMed  CAS  Google Scholar 

  • Casasanto D (2008) Who’s afraid of the big bad whorf? Crosslinguistic differences in temporal language and thought. Lang Learn 58:63–79

    Article  Google Scholar 

  • Cheng C, Fabrizio P, Ge HY, Longo VD, Li LM (2007) Inference of transcription modification in long-live yeast strains from their expression profiles. BMC Genomics 8:219

    Article  PubMed  Google Scholar 

  • Coyle S, Kroll E (2008) Starvation induces genomic rearrangements and starvation-resilient phenotypes in yeast. Mol Biol Evol 25(2):310–318

    Article  PubMed  CAS  Google Scholar 

  • Davidson G, Martin S, Boyack K, Wylie B, Martinez J, Aragon A et al (2007) Robust methods for microarray analysis. In: Akay M (ed) Genomics and proteomics engineering in medicine and biology. IEEE, NJ, pp 99–130

    Google Scholar 

  • Davidson GS, Hendrickson B, Johnson DK, Meyers CE, Wylie BN (1998) Knowledge mining with VxInsight: discovery through interaction. J Intell Inf Syst 11:259–285

    Article  Google Scholar 

  • Davidson GS, Joe RM, Roy S, Meirelles O, Allen CP, Wilson MR et al (2011) The proteomics of quiescent and nonquiescent cell differentiation in yeast stationary-phase cultures. Mol Biol Cell 22:988–998

    Article  PubMed  CAS  Google Scholar 

  • de Magalhaes JP, Budovsky A, Lehmann G, Costa J, Li Y, Fraifeld V et al (2009) The human ageing genomic resources: online databases and tools for biogerontologists. Aging Cell 8(1):65–72

    Article  PubMed  Google Scholar 

  • Drummond-Barbosa D (2008) Stem cells, their niches and the systemic environment: an aging network. Genetics 180(4):1787–1797

    Article  PubMed  Google Scholar 

  • Dunham MJ, Badrane H, Ferea T, Adams J, Brown PO, Rosenzweig F et al (2002) Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 99(25):16144–16149

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg T, Buttner S, Kroemer G, Madeo F (2007) The mitochondrial pathway in yeast apoptosis. Apoptosis 12(5):1011–1023

    Article  PubMed  CAS  Google Scholar 

  • Fabrizio P, Longo VD (2003) The chronological life span of Saccharomyces cerevisiae. Aging Cell 2:73–81

    Article  PubMed  CAS  Google Scholar 

  • Fabrizio P, Longo VD (2008) Chronological aging-induced apoptosis in yeast. Biochimica Et Biophysica Acta-Mol Cell Res 1783(7):1280–1285

    Article  CAS  Google Scholar 

  • Frohlich KU, Madeo F (2000) Apoptosis in yeast – a monocellular organism exhibits altruistic behaviour. FEBS Lett 473(1):655–660

    Article  Google Scholar 

  • Fuge EK, Braun EL, Werner-Washburne M (1994) Protein synthesis in long-term stationary-phase cultures of Saccharomyces cerevisiae. J Bact 176:5802–5813

    PubMed  CAS  Google Scholar 

  • Gonzalez C, Hadany L, Ponder RG, Price M, Hastings PJ, Rosenberg SM (2008) Mutability and importance of a hypermutable cell subpopulation that produces stress-induced mutants in Escherichia coli. PLoS Genet 4(10):e1000208

    Article  PubMed  Google Scholar 

  • Gray JV, Petsko GA, Johnston GC, Ringe D, Singer RA, Werner-Washburne M (2004) “Sleeping beauty”: quiescence in Saccharomyces cerevisiae [Review]. Microbiol Mol Biol Rev 68(2):187–206

    Article  PubMed  CAS  Google Scholar 

  • Herker E, Jungwirth H, Lehmann KA, Maldener C, Frohlich KU, Wissing S et al (2004) Chronological aging leads to apoptosis in yeast. J Cell Biol 164(4):501–507

    Article  PubMed  CAS  Google Scholar 

  • Jazwinski JM (1990) An experimental system for the molecular analysis of the aging process: the budding yeast Saccharomyces cerevisiae. J Am Gen Soc 45:B68–B74

    CAS  Google Scholar 

  • Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580

    Article  PubMed  CAS  Google Scholar 

  • Kennedy BK, Austriaco NR Jr, Zhang J, Guarente L (1995) Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80:485–496

    Article  PubMed  CAS  Google Scholar 

  • Kuningas M, Mooijaart SP, van Heemst D, Zwaan BJ, Slagboom PE, Westendorp RGJ (2008) Genes encoding longevity: from model organisms to humans. Aging Cell 7(2):270–280

    Article  PubMed  CAS  Google Scholar 

  • Laun P, Bruschi CV, Dickinson JR, Rinnerthaler M, Heeren G, Schwimbersky R et al (2007) Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing. Nucleic Acids Res 35(22):7514–7526

    Article  PubMed  CAS  Google Scholar 

  • Laun P, Pichova A, Madeo F, Heeren G, Kohlwein SD, Frohlich KU et al (2001) Aged yeast mother cells show markers of apoptosis. Yeast 18:S160

    Google Scholar 

  • Laun P, Rinnerthaler M, Bogengruber E, Heeren G, Breitenbach M (2006) Yeast as a model for chronological and reproductive aging – A comparison. Exp Gerontol 41(12):1208–1212

    Article  PubMed  CAS  Google Scholar 

  • Lewis DL, Gattie DK (1991) The ecology of quiescent microbes. ASM News 57:27–32

    Google Scholar 

  • Lewis K (2000) Programmed death in bacteria. Microbiol Mol Rev 64(3):503–533

    Article  CAS  Google Scholar 

  • Lewis K (2007) Persister cells, dormancy and infectious disease. Nat Rev Microbiol 5(1):48–56

    Article  PubMed  CAS  Google Scholar 

  • Li L, Lu Y, Qin L-X, Bar-Joseph Z, Werner-Washburne M, Breeden LL (2009) Budding yeast SSD1-V regulates transcript levels of many longevity genes and extends chronological life span in purified quiescent cells. Mol Biol Cell 20:3851–3864

    Article  PubMed  CAS  Google Scholar 

  • Longo VD (2009) Linking sirtuins, IGF-I signaling, and starvation. Exp Gerontol 44(1–2):70–74

    Article  PubMed  CAS  Google Scholar 

  • Longo VD, Ellerby LM, Bredesen DE, Valentine JS, Gralla EB (1997) Human Bcl-2 reverses survival defects in yeast lacking superoxide dismutase and delays death of wild-type yeast. J Cell Biol 137(7):1581–1588

    Article  PubMed  CAS  Google Scholar 

  • Longo VD, Fabrizio P (2002) Visions & reflections: regulation of longevity and stress resistance: a molecular strategy conserved from yeast to humans? Cell Mol Life Sci 59(6):903–908

    Article  PubMed  CAS  Google Scholar 

  • Lopez D, Vlamakis H, Kolter R (2009) Generation of multiple cell types in Bacillus subtilis. FEMS Microbiol Rev 33(1):152–163

    Article  PubMed  CAS  Google Scholar 

  • Madeo F, Engelhardt S, Herker E, Lehmann N, Maldener C, Proksch A et al (2002) Apoptosis in yeast: a new model system with applications in cell biology and medicine. Curr Genet 41(4):208–216

    Article  PubMed  CAS  Google Scholar 

  • Madeo F, Frohlich E, Frohlich KU (1997) A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 139:729–734

    Article  PubMed  CAS  Google Scholar 

  • Madia F, Wei M, Yuan V, Hu J, Gattazzo C, Pham P et al (2009) Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Pol{zeta}-dependent mechanism. J Cell Biol 186:509–523

    Article  PubMed  CAS  Google Scholar 

  • Martinez MJ, Roy S, Archuletta AB, Wentzell PD, Anna-Arriola SS, Rodriguez A et al (2004) Genomic analysis of stationary-phase and exit in Saccharomyces cerevisiae: gene expression and identification of novel essential genes. Mol Biol Cell 15:5295–5305

    Article  PubMed  CAS  Google Scholar 

  • Minois N, Frajnt M, Wilson C, Vaupel JW (2005) Advances in measuring lifespan in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci USA 102(2):402–406

    Article  PubMed  CAS  Google Scholar 

  • Minois N, Lagona F, Frajnt M, Vaupel JW (2009) Plasticity of death rates in stationary phase in Saccharomyces cerevisiae. Aging Cell 8(1):36–44

    Article  PubMed  CAS  Google Scholar 

  • Moore JK, Miller RK (2007) The cyclin-dependent kinase Cdc28p regulates multiple aspects of Kar9p function in yeast. Mol Biol Cell 18(4):1187–1202

    Article  PubMed  CAS  Google Scholar 

  • Mota M, Soares EV (1994) Poplulation dynamics of flocculating yeasts. FEMS Microbiol Rev 14:45–52

    Article  PubMed  CAS  Google Scholar 

  • Narbonne P, Roy R (2006) Regulation of germline stem cell proliferation downstream of nutrient sensing. Cell Div 1:1–29

    Google Scholar 

  • Nayak BB, Kamiya E, Nishino T, Wada M, Nishimura M, Kogure K (2005) Separation of active and inactive fractions from starved culture of Vibrio parahaemolyticus by density dependent cell sorting. FEMS Microbiol Ecol 51(2):179–186

    Article  PubMed  CAS  Google Scholar 

  • Nishino T, Nayak BB, Kogure K (2003) Density-dependent sorting of physiologically different cells of Vibrio parahaemolyticus. Appl Environ Microbiol 69(6):3569–3572

    Article  PubMed  CAS  Google Scholar 

  • Paaby AB, Schmidt PS (2009) Dissecting the genetics of longevity in Drosophila melanogaster. Fly 3(1):29–38

    Article  PubMed  CAS  Google Scholar 

  • Parrella E, Longo VD (2008) The chronological life span of Saccharomyces cerevisiae to study mitochondrial dysfunction and disease. Methods 46(4):256–262

    Article  PubMed  CAS  Google Scholar 

  • Powers RW, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 20(2):174–184

    Article  PubMed  CAS  Google Scholar 

  • Qin H, Lu M, Goldfarb D (2008) Genomic instability is associated with natural life span variation in Saccharomyces cerevisiae. PLoS One 3:e2670

    Article  PubMed  Google Scholar 

  • Rockenfeller P, Madeo F (2008) Apoptotic death of ageing yeast. Exp Gerontol 43(10):876–881

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg SM (2009) Life, death, differentiation, and the multicellularity of Bacteria. PLoS Genet 5(3):e1000418

    Article  PubMed  Google Scholar 

  • Rossi DJ, Jamieson CHM., Weissman IL (2008) Stems cells and the pathways to aging and cancer. Cell 132(4):681–696

    Article  PubMed  CAS  Google Scholar 

  • Shimokawa I, Chiba T, Yamaza H, Komatsu T (2008) Longevity genes: insights from calorie restriction and genetic longevity models. Mol Cells 26(5):427–435

    PubMed  CAS  Google Scholar 

  • Sinclair D, Mills K, Guarente L (1998) Aging in Saccharomyces cerevisiae. Annu Rev Microbiol 52:533–560

    Article  PubMed  CAS  Google Scholar 

  • Sniegowski PD (1995) The origin of adaptive mutants: random or nonrandom? J Mol Evol 40:94–101

    Article  CAS  Google Scholar 

  • Soares EV, Mota M (1996) Flocculation onset, growth phase, and genealogical age in Saccharomyces cerevisiae. Can J Microbiol 42:539–547

    Article  PubMed  CAS  Google Scholar 

  • Stratford M (1993) Yeast flocculation: flocculation onset and receptor availability. Yeast 9(1):85–94

    Article  PubMed  CAS  Google Scholar 

  • Sundin GW, Weigand MR (2007) The microbiology of mutability [Review]. FEMS Microbiol Lett 277(1):11–20

    Article  PubMed  CAS  Google Scholar 

  • Thorpe PH, Bruno J, Rothstein R (2009) Kinetochore asymmetry defines a single yeast lineage. Proc Natl Acad Sci USA 106:6673–6678

    Article  PubMed  CAS  Google Scholar 

  • Wallenfang MR (2007) Aging within the stem cell niche. Dev Cell 13(5):603–604

    Article  PubMed  CAS  Google Scholar 

  • Warren LA, Rossi DJ (2009) Stem cells and aging in the hematopoietic system. Mech Ageing Dev 130(1–2):46–53

    Article  PubMed  CAS  Google Scholar 

  • Waskar M, Li YS, Tower J (2005) Stem cell aging in the Drosophila ovary. Age 27(3):201–212

    Article  CAS  Google Scholar 

  • Wei M, Fabrizio P, Hu J, Ge HY, Cheng C, Li L et al (2008) Life span extension by calorie restriction depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9. PLoS Genet 4(1):e13

    Article  PubMed  Google Scholar 

  • Werner-Washburne M, Braun E, Johnston GC, Singer RA (1993) Stationary phase in the yeast Saccharomyces cerevisiae. Microbiol Rev 57:383–401

    PubMed  CAS  Google Scholar 

  • Werner-Washburne M, Brown D, Braun E (1991) Bcy1, the regulatory subunit of cAMP-dependent protein kinase in yeast, is differentially modified in response to the physiological status of the cell. J Biol Chem 266(29):19704–19709

    PubMed  CAS  Google Scholar 

  • Werner-Washburne M, Stone DE, Craig EA (1987) Complex interactions among members of an essential subfamily of hsp70 genes in Sacccharomyces cerevisiae. Mol Cell Biol 7(7):2568–2577

    PubMed  CAS  Google Scholar 

  • Werner-Washburne M, Wylie B, Boyack K, Fuge E, Galbraith J, Weber J et al (2002) Comparative analysis of multiple genome-scale data sets. Genome Res 12(10):1564–1573

    Article  PubMed  CAS  Google Scholar 

  • Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B et al (1999) Functional characterization of the S-cerevisiae genome by gene deletion and parallel analysis. Science 285(5429):901–906

    Article  PubMed  CAS  Google Scholar 

  • Wolkow CA (2002) Life span: getting the signal from the nervous system [Review]. Trends Neurosci 25(4):212–216

    Article  PubMed  CAS  Google Scholar 

  • Zaman S, Lippman SI, Zhao X, Broach JR (2008) How Saccharomyces responds to nutrients. Annu Rev Genet 42:27–81

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank all the people who have helped us think about this; Frank Madeo for reviewing the manuscript; and Santos Salinas-Contreras for helping with the figures. This work was funded by a grant from NSF: MCB0645854. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy’s National Nuclear Security Administration under Contract DE-AC04-94AL85000.

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Authors and Affiliations

  1. Department of Biology, University of New Mexico, Albuquerque, NM, 87131, USA

    M. Werner-Washburne & George S. Davidson

  2. Broad Institute, 7 Cambridge Center, Cambridge, MA, 02142, USA

    Sushmita Roy

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  1. M. Werner-Washburne
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  2. Sushmita Roy
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  3. George S. Davidson
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Correspondence to M. Werner-Washburne .

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Editors and Affiliations

  1. , Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Michael Breitenbach

  2. , Tulane Center for Aging and Department o, Tulane University Health Sciences Center, Tulane Avenue SL-12 1430, New Orleans, 70112, Louisiana, USA

    S. Michal Jazwinski

  3. , Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, Salzburg, 5020, Austria

    Peter Laun

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Werner-Washburne, M., Roy, S., Davidson, G.S. (2011). Aging and the Survival of Quiescent and Non-quiescent Cells in Yeast Stationary-Phase Cultures. In: Breitenbach, M., Jazwinski, S., Laun, P. (eds) Aging Research in Yeast. Subcellular Biochemistry, vol 57. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2561-4_6

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