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Updated: Apr 26, 2026
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A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
Published on: September 17, 2020
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Inferring Gene Regulatory Network Architecture Underlying Complex Traits: An Integrative Analysis of Mutant Lifespan
Meng Ma1,2, Juan Long1,2, Yuting Chen2
1Department of Health Management & Institute of Health Management, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Aging Cell
|April 25, 2026
Summary
This study reveals a layered gene network architecture influencing aging. Master regulators (MRs) connect peripheral genes to core gene functional modules, impacting lifespan and offering insights into complex traits.
Area of Science:
- Genetics
- Systems Biology
- Aging Research
Background:
- Complex phenotypes like aging involve intricate gene regulatory networks.
- Distinguishing between core genes directly impacting traits and peripheral genes indirectly influencing them is challenging.
- A layered network architecture, with core and peripheral genes, has been proposed but lacks empirical validation.
Purpose of the Study:
- To develop and validate an approach for inferring gene network architecture underlying complex traits, using yeast aging as a model.
- To identify master regulators (MRs) that significantly influence lifespan.
- To characterize the relationship between peripheral genes, MRs, and core gene functional modules in trait determination.
Main Methods:
- Analysis of yeast deletion mutant lifespans and gene expression profiles.
- Identification of MRs by correlating gene expression changes with lifespan variations.
- Experimental validation of predicted MRs.
- Defining peripheral genes based on their effects being explainable by MRs.
- Analysis of functional modules (groups of core genes) affected by MRs.
Main Results:
- Identified MRs whose expression changes correlate with lifespan.
- Experimentally validated a high proportion of predicted lifespan-extending MRs.
- Defined peripheral genes and demonstrated their connection to MRs.
- Discovered functional modules (e.g., stress response, autophagy) altered by MRs, validating the layered network model.
- Showcased a network architecture: peripheral genes → MRs → functional modules of core genes → lifespan.
Conclusions:
- The study successfully infers and validates a layered gene regulatory network architecture for complex traits like aging.
- The identified MRs and functional modules provide mechanistic insights into lifespan regulation in yeast.
- The developed approach is generalizable and applicable to analyzing complex human traits using diverse biological data.
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