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Updated: Mar 24, 2026

Quantification of Information Encoded by Gene Expression Levels During Lifespan Modulation Under Broad-range Dietary Restriction in C. elegans
Published on: August 16, 2017
A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction
1Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Dietary restriction (DR) extends lifespan by altering metabolism and cell cycle. Targeting key DR regulators can mimic and even enhance DR
Area of Science:
- Aging and longevity research
- Genetics and molecular biology
- Systems biology
Background:
- Dietary restriction (DR) is a potent lifespan-extending intervention.
- Existing genetic interventions do not fully replicate DR's effects.
- A unified regulatory system for diverse DR regimens remains unknown.
Purpose of the Study:
- To elucidate the temporal gene expression dynamics of DR.
- To identify key regulatory modules governing DR responses.
- To engineer genetic interventions that fully recapitulate DR.
Main Methods:
- Temporally resolved transcriptomic analysis in Caenorhabditis elegans under calorie restriction and intermittent fasting.
- Network module identification based on regulator target specificity.
- Genetic manipulation of identified regulatory nodes.
Main Results:
- Early DR responses involve metabolic pathways; late responses involve cell cycle and DNA damage.
- Three distinct network modules of DR regulators were uncovered.
- Perturbing multiple modules progressively mimicked DR transcriptomes.
- Simultaneous targeting of all three modules resulted in extreme lifespan extension and DR refractoriness.
Conclusions:
- DR involves complex, temporally segregated regulatory networks.
- Feedback controls among DR regulators can be leveraged.
- A unified system can drive regulatory circuitry to a younger steady state, mimicking DR's full effects.

