Research Articles:
Microbial Cell, Vol. 12, No. 1, pp. 274 - 289; doi: 10.15698/mic2025.10.861
The core genetic drivers of chronological aging in yeast are universal regulators of longevity
1 Unidad de Genómica Avanzada, Cinvestav, 36824 Irapuato, Mexico. 2 Centro de Investigación sobre el Envejecimiento, Cinvestav, 14330 Tlalpan, Cd.Mx., Mexico. 3 Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 Coyoacán, Cd.Mx., Mexico. 4 Institute of Ecology and Evolution, The University of Edinburgh, EH9 3FL Edinburgh, UK.
Keywords: chronological lifespan, genome-wide mutant screening, functional genomics meta-analysis, genetic interactions, Saccharomyces cerevisiae.
Received originally: 25/03/2025 Received in revised form: 06/08/2025
Accepted: 11/08/2025
Published: 31/10/2025
Correspondence:
Alexander DeLuna, alexander.deluna@cinvestav.mx
Conflict of interest statement: The authors declare that they have no conflict of interest.
Please cite this article as: Erika Cruz-Bonilla, Sergio E. Campos, Soledad Funes, Cei Abreu-Goodger and Alexander DeLuna (2025). The core genetic drivers of chrono-logical aging in yeast are universal regulators of longevity. Microbial Cell 12: 274-289. doi: 10.15698/mic2025.10.861
Abstract
The chronological lifespan of Saccharomyces cerevisiae has significantly contributed to our understanding of aging in eukaryotic cells. However, gaining a genome-wide perspective of this trait remains challenging due to substantial discrepancies observed across genome-wide gene-deletion screens. In this study, we systematically compiled nine chronological-lifespan datasets and evaluated how shared experimental variables influenced screen variability. Furthermore, we performed a meta-analysis to compile a ranked catalog of key processes and regulators driving chronological longevity in yeast, ensuring their robustness across diverse experimental setups. These consistent chronological aging factors were enriched in genes associated with yeast replicative lifespan and orthologs implicated in aging across other model organisms. Functional analysis revealed that the downstream cellular mechanisms underlying chronological longevity in yeast align with well-established, universal hallmarks of aging. Importantly, we identified transcriptional regulators associated with these consistent genetic factors, uncovering potential global and local modulators of chronological aging. Our findings provide an integrated view of the core genetic landscape underlying aging in yeast, highlighting the value of the chronological lifespan paradigm for investigating conserved mechanisms of aging.
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AUTHOR CONTRIBUTIONS
E.C-B. and A.D. conceptualized and designed the study. E.C-B. and S.C. performed experiments. E.C-B. performed data analysis. S.F. and A.D. oversaw experiments. C.A-G. and A.D. oversaw data analysis. S.F. and A.D. acquired funding. E.C-B. and A.D. wrote the original draft. All authors read and critically revised the manuscript.
ACKNOWLEDGMENTS
We thank Mayra Flores-Barraza and Ariann E. Mendoza-Martínez for technical support and Diana Ascencio and J. Abraham Avelar-Rivas for critical reading of the manuscript. This work was funded by the Secretaría de Ciencia, Humanidades, Tecnología e Inno-vación de México (Secihti), Grants CB2015/254365, CF-2009-G-103000, and CF-2023-I-1545. E.C-B. was funded by doctoral fel-lowship CVU 711011 from Secihti. A.D. was funded by a sabbati-cal fellowship CVU 26244 from Secihti.
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© 2025
The core genetic drivers of chronological aging in yeast are universal regulators of longevity by Cruz-Bonilla et al. is licensed under a Creative Commons Attribution 4.0 International License.
