AsianScientist (Mar. 22, 2016) – Researchers in China have made significant inroads into reversing engineered life-span extension in roundworms by dietary restriction. Their work was published in Cell Metabolism.
Dietary restriction (DR) as a means to extend lifespan across multiple organisms has been studied extensively for its benefits in aging. Although several genes and pathways related to nutrition sensing and stress response can mediate responses to DR regimens, no single genetic intervention has been able to recreate the full effects of DR. Furthermore, the mechanisms behind why DR is so effective remain unclear.
The team of scientists led by Professor Han Jing-Dong Jackie and colleagues from the CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, first obtained temporally resolved transcriptomes during calorie restriction and intermittent fasting in roundworms and found that early and late responses involve metabolism and cell cycle/DNA damage respectively.
Then, by using a new network inference algorithm to integrate the newly generated transcriptome data with genetically perturbed transcriptome data in public domains, they uncovered three network modules of DR regulators by target specificity.
By genetic manipulations of nodes representing discrete modules, they found that the transcriptomes of young adult worms progressively resemble DR as multiple nodes are perturbed. Targeting all three nodes simultaneously resulted in extremely long-lived animals that are refractory to DR.
These results and dynamic simulations demonstrate that extensive feedback controls among regulators may be leveraged to drive the regulatory circuitry to a younger steady state, recapitulating the full effect of DR.
This work also epitomized a new systems biological framework for reverse engineered regulatory networks and identified key regulatory mechanisms for aging, dietary intervention and other complex biological processes.
The article can be found at: Lei et al. (2016) A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
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Source: Chinese Academy of Sciences; Photo: Shutterstock.
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