ArticleProceedings of the National Academy of Sciences of the United States of America2009
A network biology approach to aging in yeast.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Computational Systems Biology Approaches to Cellular Aging - Integrating Network Maps and Dynamical Models.Quantitative biology (Beijing, China) · 2025Article
- The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism.Science advances · 2025Article
- Current Challenges in Plant Systems Biology.Advances in experimental medicine and biology · 2021Article
- Identifiability and experimental design in perturbation studies.Bioinformatics (Oxford, England) · 2020Article
- Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila.PLoS genetics · 2020Article
- Divergent Aging of Isogenic Yeast Cells Revealed through Single-Cell Phenotypic Dynamics.Cell systems · 2019Article
- Conventional and emerging roles of the energy sensor Snf1/AMPK inMicrobial cell (Graz, Austria) · 2018Review
- The role of autophagy in the regulation of yeast life span.Annals of the New York Academy of Sciences · 2018Review
- Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation.Microbial cell (Graz, Austria) · 2016Article
- The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation.Cell cycle (Georgetown, Tex.) · 2016Article
- Review
- On predicting regulatory genes by analysis of functional networks in C. elegans.BioData mining · 2015Article
- Proteasomes, Sir2, and Hxk2 form an interconnected aging network that impinges on the AMPK/Snf1-regulated transcriptional repressor Mig1.PLoS genetics · 2015Article
- Cell-autonomous mechanisms of chronological aging in the yeastMicrobial cell (Graz, Austria) · 2014Review
- Longevity pathways and maintenance of the proteome: the role of autophagy and mitophagy during yeast ageing.Microbial cell (Graz, Austria) · 2014Review
- Gene differential coexpression analysis based on biweight correlation and maximum clique.BMC bioinformatics · 2014Article
- Article
- Identification of the dichotomous role of age-related LCK in calorie restriction revealed by integrative analysis of cDNA microarray and interactome.Age (Dordrecht, Netherlands) · 2013Article
- Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review.Pharmacology & therapeutics · 2013Review
- Genome-scale studies of aging: challenges and opportunities.Current genomics · 2012Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
In this study, a reverse-engineering strategy was used to infer and analyze the structure and function of an aging and glucose repressed gene regulatory network in the budding yeast Saccharomyces cerevisiae. The method uses transcriptional perturbations to model the functional interactions between genes as a system of first-order ordinary differential equations. The resulting network model correctly identified the known interactions of key regulators in a 10-gene network from the Snf1 signaling pathway, which is required for expression of glucose-repressed genes upon calorie restriction. The majority of interactions predicted by the network model were confirmed using promoter-reporter gene fusions in gene-deletion mutants and chromatin immunoprecipitation experiments, revealing a more complex network architecture than previously appreciated. The reverse-engineered network model also predicted an unexpected role for transcriptional regulation of the SNF1 gene by hexose kinase enzyme/transcriptional repressor Hxk2, Mediator subunit Med8, and transcriptional repressor Mig1. These interactions were validated experimentally and used to design new experiments demonstrating Snf1 and its transcriptional regulators Hxk2 and Mig1 as modulators of chronological lifespan. This work demonstrates the value of using network inference methods to identify and characterize the regulators of complex phenotypes, such as aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.