The core genetic drivers of chronological aging in yeast are universal regulators of longevity
Authors:Erika Cruz-Bonilla1, Sergio E. Campos2, Soledad Funes3, Cei Abreu-Goodger4 and Alexander DeLuna1,2,*
doi: 10.15698/mic2025.10.861
Volume 12, pp. 274 to 289, published 31/10/2026.
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
Corresponding Author(s):
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
© 2025 Cruz-Bonilla et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
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.