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In silico drug screen in mouse liver identifies candidate calorie restriction mimetics
Kristen Fortney1, Eric K Morgen, Max Kotlyar
1Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Abstract:
Calorie restriction (CR) extends life span in mammals and delays the onset of age-related diseases, including cancer and diabetes. Drugs that target the same genes and pathways as CR may have enormous therapeutic potential. Recently, genome-scale data on the responses of human cell lines to over 1,000 drug treatments have become available. Here we integrate these data with gene expression signatures of CR in mouse liver to generate a prioritized list of candidate CR mimetics. We identify 14 drugs that reproduce the effects of CR at the transcriptional level.
Insights
Calorie restriction (CR) extends lifespan and delays age-related diseases. Researchers identified 14 drugs that mimic CR's effects on gene expression, offering potential therapeutic benefits.
Area of Science:
- Gerontology and Molecular Biology
- Drug Discovery and Development
Background:
- Calorie restriction (CR) is known to extend lifespan and mitigate age-related diseases like cancer and diabetes in mammals.
- Understanding the molecular mechanisms of CR can reveal therapeutic targets for aging and disease.
- Recent advances provide large-scale data on human cellular responses to drug treatments.
Purpose of the Study:
- To identify potential drug candidates that mimic the life-extending and disease-delaying effects of calorie restriction.
- To leverage genome-scale drug response data and CR gene expression signatures for drug discovery.
Main Methods:
- Integration of genome-scale drug response data from human cell lines with gene expression signatures of CR in mouse liver.
- Prioritization of candidate drugs based on their ability to replicate CR's transcriptional effects.
Main Results:
- A prioritized list of 14 candidate drugs was generated.
- These drugs were identified as potentially reproducing the effects of calorie restriction at the transcriptional level.
Conclusions:
- The study successfully identified drugs that may act as CR mimetics.
- These findings open avenues for developing therapeutics that target aging and related diseases by mimicking CR's molecular pathways.
