Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae
Open accessAbstract
Aging is believed to be a nonadaptive process that escapes the force of natural selection. Here, we challenge this dogma by showing that yeast laboratory strains and strains isolated from grapes undergo an age- and pH-dependent death with features of mammalian programmed cell death (apoptosis). After 90-99% of the population dies, a small mutant subpopulation uses the nutrients released by dead cells to grow. This adaptive regrowth is inversely correlated with protection against superoxide toxicity and life span and is associated with elevated age-dependent release of nutrients and increased mutation frequency. Computational simulations confirm that premature aging together with a relatively high mutation frequency can result in a major advantage in adaptation to changing environments. These results suggest that under conditions that model natural environments, yeast organisms undergo an altruistic and premature aging and death program, mediated in part by superoxide. The role of similar pathways in the regulation of longevity in organisms ranging from yeast to mice raises the possibility that mammals may also undergo programmed aging.
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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 Fabrizio 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 Fabrizio et al., 2004
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 Fabrizio 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 Fabrizio 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 Fabrizio et al., 2004
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References 38 · Cited by 355
Research works printed but not linked: 1
- Longo, V. 1997. The chronological life span of Saccharomyces cerevisiae. Studies of superoxide dismutase, Ras and Bcl-2. Ph.D. thesis. University of California, Los Angeles, CA. 179 pp.
- Authors
- Fabrizio, P., Battistella, L., Vardavas, R., Gattazzo, C., Liou, L.-L., Diaspro, A., Dossen, J. W., Gralla, E. B., & Longo, V. D.
- Affiliations
- University of Southern California (US)
- University of California, Los Angeles (US)
- University of Genoa (IT)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2004-09-27
- Volume
- 166
- Issue
- 7
- Pages
- 1055-1067
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2172019
- OpenAlex
- W2081490071
- Cited by
- 355
- References
- 38
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 6 · 2020: 14 · 2019: 10 · 2018: 19 · 2017: 12 · 2016: 17 · 2015: 14 · 2014: 11 · 2013: 24 · 2012: 33
- FWCI
- 6.84
- 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)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Funders
- National Institute on Aging (AG20642, R01AG020642)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- superoxide, programmed aging, altruism, programmed cell death, apoptosis, Saccharomyces cerevisiae, yeast aging, lifespan, mutation frequency, nutrient cycling, adaptive evolution, premature aging, longevity
- MeSH terms
- Adaptation, Physiological, Aging, Cell Survival, Cells, Cultured, Culture Media, Environment, Hydrogen Peroxide, Mutation, Saccharomyces cerevisiae, Species Specificity, Starvation, Superoxides, Apoptosis, Oxidative Stress, Aging, Premature
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