Chronological aging leads to apoptosis in yeast
Open accessAbstract
During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone.
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Features like superoxide levels and regrowth frequency are connected to PCD, an adaptive mechanism required for programmed aging through selective advantage at least in yeast.
“Features like superoxide levels and regrowth frequency are connected to PCD, an adaptive mechanism required for programmed aging through selective advantage at least in yeast (Fabrizio et al., 2004; Herker et al., 2004).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Herker et al., 2004
Genetic disruption of PCD-mediated cell removal improves short-term survival of aged cultures; however, the surviving cells lose their ability to re-grow, indicating an accumulation of damaged cells in the absence of PCD.
“Genetic disruption of PCD-mediated cell removal improves short-term survival of aged cultures; however, the surviving cells lose their ability to re-grow, indicating an accumulation of damaged cells in the absence of PCD (Fabrizio et al., 2004; Herker et al., 2004).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Herker et al., 2004
Within chronologically aged yeast cultures, single yeast cells induce programmed cell death (PCD) as a result of the accumulation of oxygen radicals and metacaspase activation.
“Within chronologically aged yeast cultures, single yeast cells induce programmed cell death (PCD) as a result of the accumulation of oxygen radicals and metacaspase activation (Fabrizio et al., 2004; Herker et al., 2004).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Herker et al., 2004
Strains with dysfunctional PCD have an initial advantage but are eventually overgrown and outcompeted by wild type cells.
“Strains with dysfunctional PCD have an initial advantage but are eventually overgrown and outcompeted by wild type cells (Fabrizio et al., 2004; Herker et al., 2004).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Herker et al., 2004
Deletion of the S. cerevisiae metacaspase YCA1 increased resistance to PCD caused by stressors such as hydrogen peroxide and also increased chronological life span.
“Deletion of the Saccharomyces cerevisiae metacaspase YCA1 increased resistance to PCD caused by stressors such as hydrogen peroxide and also increased chronological life span (Herker et al., 2004; Madeo et al., 2002).”
From Programmed cell death in aging (2015) · cites this paper as Herker et al., 2004
Cell death in the S. cerevisiae chronological aging assay has been described as a PCD based on both morphological and genetic criteria.
“Cell death in the Saccharomyces cerevisiae chronological aging assay has also been described as a PCD based on both morphological and genetic criteria (Fabrizio et al., 2004; Herker et al., 2004).”
From Programmed cell death in aging (2015) · cites this paper as Herker et al., 2004
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Cites
Martin, S. J., Reutelingsperger, C. P., McGahon, A. J., Rader, J. A., van Schie, R. C., LaFace, D. M., & Green, D. R. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.5.1545 · Cited by 2,824 · see citing works
Mechanisms and Genes of Cellular Suicide
Steller, H. (1995) · Science · doi:10.1126/science.7878463 · Cited by 2,465 · see citing works
Oxygen Stress: A Regulator of Apoptosis in Yeast
Madeo, F., Fröhlich, E., Ligr, M., Grey, M., Sigrist, S. J., Wolf, D. H., & Fröhlich, K. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.4.757 · Cited by 1,017 · see citing works
Self-citationA Caspase-Related Protease Regulates Apoptosis in Yeast
Madeo, F., Herker, E., Maldener, C., Wissing, S., Lächelt, S., Herlan, M., Fehr, M., Lauber, K., Sigrist, S. J., Wesselborg, S., et al. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00501-4 · Cited by 873 · see citing works
Self-citationA Yeast Mutant Showing Diagnostic Markers of Early and Late Apoptosis
Madeo, F., Fröhlich, E., & Fröhlich, K. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.3.729 · Cited by 794 · see citing works
Self-citationSynergistic Roles for Pim-1 and c-Myc in STAT3-Mediated Cell Cycle Progression and Antiapoptosis
Shirogane, T., Fukada, T., Müller, J. M. M., Shima, D. T., Hibi, M., & Hirano, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80145-4 · Cited by 427 · see citing works
Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis
Laun, P., Pichová, A., Madeo, F., Fuchs, J., Ellinger, A., Kohlwein, S. D., Dawes, I. W., Fröhlich, K., & Breitenbach, M. (2001) · Molecular Microbiology · doi:10.1111/j.1365-2958.2001.02317.x · Cited by 416 · see citing works
Self-citationLudovico, P., Rodrigues, F. J. S., Almeida, A. J., Silva, M. T., Barrientos, A., & Côrte‐Real, M. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e01-12-0161 · Cited by 377 · see citing works
Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins.Preprint
Moye-Rowley, S., Harshman, K., & Parker, C. S. (1989) · Genes & Development · doi:10.1101/gad.3.3.283 · Cited by 333 · see citing works
Longo, V. D., Ellerby, L., Bredesen, D. E., Valentine, J. S., & Gralla, E. B. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.7.1581 · Cited by 209 · see citing works
Pungerčar, J. R., Kopitar‐Jerala, N., Bogyo, M. S., Türk, V., Vasiljeva, O. S., Štefe, I., Vandenabeele, P., Brömme, D., Puizdar, V., Fonovič, M., et al. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401247 · Cited by 197 · see citing works
MacLean, M. J., Harris, N., & Piper, P. W. (2001) · Yeast · doi:10.1002/yea.701 · Cited by 139 · see citing works
Analysis of Saccharomyces cerevisiae proteins induced by peroxide and superoxide stress
Jamieson, D. J., Rivers, S. L., & Stephen, D. W. S. (1994) · Microbiology · doi:10.1099/13500872-140-12-3277 · Cited by 131 · see citing works
Wendler, F., Bergler, H., Prutej, K., Jungwirth, H., Zisser, G., Kuchler, K., & Högenauer, G. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.43.27091 · Cited by 84 · see citing works
Self-citationTargeted Destruction of DNA Replication Protein Cdc6 by Cell Death Pathways in Mammals and Yeast
Blanchard, F., Rusiniak, M. E., Sharma, K., Sun, X., Todorov, I., Castellano, M. M., Gutiérrez, C., Baumann, H., & Burhans, W. C. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-02-0010 · Cited by 76 · see citing works
Mazzoni, C., Mancini, P., Verdone, L., et al. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-05-0258 · Cited by 68 · see citing works
Evidence for cooperation between cells during sporulation of the yeast Saccharomyces cerevisiae.
Jakubowski, H., & Goldman, E. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.12.5166 · Cited by 26 · see citing works
Diazaborine Treatment of Baker's Yeast Results in Stabilization of Aberrant mRNAs
Jungwirth, H., Bergler, H., & Högenauer, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104487200 · Cited by 17 · see citing works
Self-citationEvidence for Cooperation Between Cells During Sporulation of the Yeast Saccharomyces cerevisiae
Jakubowski, H., & Goldman, E. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.12.5166-5178.1988 · Cited by 6 · see citing works
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Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1975 · Cited by 1,680 · see citing works
Replicative and chronological aging in Saccharomyces cerevisiae
Longo, V. D., Shadel, G. S., Kaeberlein, M., & Kennedy, B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.002 · Cited by 595 · see citing works
Programmed cell death in aging
Tower, J. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.04.002 · Cited by 426 · see citing works
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Temple, M. D., Perrone, G. G., & Dawes, I. W. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.04.003 · Cited by 398 · see citing works
Superoxide is a mediator of an altruistic aging program in <i>Saccharomyces cerevisiae</i>
Fabrizio, P., Battistella, L., Vardavas, R., Gattazzo, C., Liou, L.-L., Diaspro, A., Dossen, J. W., Gralla, E. B., & Longo, V. D. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200404002 · Cited by 355 · see citing works
The Search for Antiaging Interventions: From Elixirs to Fasting Regimens
de Cabo, R., Carmona-Gutierrez, D., Bernier, M., Hall, M. N., & Madeo, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.031 · Cited by 345 · see citing works
Self-citationEndonuclease G Regulates Budding Yeast Life and Death
Büttner, S., Eisenberg, T., Carmona-Gutierrez, D., Ruli, D., Knauer, H., Ruckenstuhl, C., Sigrist, C., Wissing, S., Kollroser, M., Fröhlich, K.-U., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.12.021 · Cited by 331 · see citing works
Self-citationRecent developments in yeast aging
Kaeberlein, M., Burtner, C. R., & Kennedy, B. K. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030084 · Cited by 239 · see citing works
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Büttner, S., Ruli, D., Vögtle, F., Galluzzi, L., Moitzi, B., Eisenberg, T., Kepp, O., Habernig, L., Carmona‐Gutierrez, D., Rockenfeller, P., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.197 · Cited by 133 · see citing works
Self-citationAndrés, M. T., Viejo-Díaz, M., & Fierro, J. F. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01597-07 · Cited by 114 · see citing works
The propeptide of yeast cathepsin D inhibits programmed necrosis
Carmona-Gutiérrez, D., Bauer, M. A., Ring, J., Knauer, H., Eisenberg, T., Büttner, S., Ruckenstuhl, C., Reisenbichler, A., Magnes, C., Rechberger, G. N., et al. (2011) · Cell Death & Disease · doi:10.1038/cddis.2011.43 · Cited by 69 · see citing works
Self-citationDudgeon, D. D., Zhang, N., Ositelu, O. O., Kim, H., & Cunningham, K. W. (2008) · Eukaryotic Cell · doi:10.1128/ec.00291-08 · Cited by 59 · see citing works
Mitochondrial respiration and reactive oxygen species in mitochondrial aging mutants
SEDENSKY, M., & GMORGAN, P. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.01.004 · Cited by 57 · see citing works
Gyetvai, Ã., Emri, T., Takács, K., Dergez, T., Fekete, A., Pesti, M., Pócsi, I., & Lenkey, B. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00097.x · Cited by 53 · see citing works
Briones-Martin-del-Campo, M., Orta-Zavalza, E., Cañas-Villamar, I., Gutiérrez-Escobedo, G., Juárez-Cepeda, J., Robledo-Márquez, K., Arroyo-Helguera, O., Castaño, I., & De Las Peñas, A. (2015) · Microbiology · doi:10.1099/mic.0.000006 · Cited by 29 · see citing works
- Authors
- Herker, E., Jungwirth, H., Lehmann, K. A., Maldener, C., Fröhlich, K.-U., Wissing, S., Büttner, S., Fehr, M., Sigrist, S., & Madeo, F.
- Affiliations
- University of Tübingen (DE)
- 2Wilhelm-Schickard Institute for Informatics, University of Tübingen, 72076 Tübingen, Germany
- 4Institute of Molecular Biology, Biochemistry, and Microbiology, Karl-Franzens University, 8010 Graz, Austria
- 1Institute for Physiological Chemistry, University of Tübingen, 72076 Tübingen, Germany
- Carnegie Institution for Science (US)
- European Neuroscience Institute Göttingen (DE)
- Corresponding author
- Madeo, Frank
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-02-16
- Volume
- 164
- Issue
- 4
- Pages
- 501-507
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2171996
- OpenAlex
- W2067820742
- Cited by
- 548
- References
- 19
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 17 · 2021: 19 · 2020: 20 · 2019: 26 · 2018: 21 · 2017: 15 · 2016: 21 · 2015: 17 · 2014: 23 · 2013: 22 · 2012: 39
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- chronological aging, apoptosis, yeast, YAP, caspase activation, oxygen free radicals, cell suicide, clonal competition, unicellular organisms
- MeSH terms
- Aging, Cell Survival, Enzyme Activation, Saccharomyces cerevisiae, Transcription Factors, Biomarkers, Apoptosis, Reactive Oxygen Species, Caspases, Saccharomyces cerevisiae Proteins
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