Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics
Abstract Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of t...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56196-z |
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| author | Anaïs Rat Veronica Martinez Fernandez Marie Doumic Maria Teresa Teixeira Zhou Xu |
| author_facet | Anaïs Rat Veronica Martinez Fernandez Marie Doumic Maria Teresa Teixeira Zhou Xu |
| author_sort | Anaïs Rat |
| collection | DOAJ |
| description | Abstract Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells’ shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations—from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape. |
| format | Article |
| id | doaj-art-2993c42889a749058452ea08951c145b |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2993c42889a749058452ea08951c145b2025-01-26T12:42:03ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-025-56196-zMathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamicsAnaïs Rat0Veronica Martinez Fernandez1Marie Doumic2Maria Teresa Teixeira3Zhou Xu4Aix Marseille Univ, CNRS, I2M, Centrale MarseilleSorbonne Université, CNRS, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, LBMCESorbonne Université, CNRS, Université de Paris, Inria, Laboratoire Jacques-Louis Lions UMR7598Sorbonne Université, CNRS, Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, LBMCESorbonne Université, CNRS, Laboratory of Computational and Quantitative Biology, LCQBAbstract Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells’ shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations—from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape.https://doi.org/10.1038/s41467-025-56196-z |
| spellingShingle | Anaïs Rat Veronica Martinez Fernandez Marie Doumic Maria Teresa Teixeira Zhou Xu Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics Nature Communications |
| title | Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics |
| title_full | Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics |
| title_fullStr | Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics |
| title_full_unstemmed | Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics |
| title_short | Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics |
| title_sort | mathematical model linking telomeres to senescence in saccharomyces cerevisiae reveals cell lineage versus population dynamics |
| url | https://doi.org/10.1038/s41467-025-56196-z |
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