A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.

ABSTRACT: Dietary restriction (DR) is the most powerful natural means to extend lifespan. Although several genes can mediate responses to alternate DR regimens, no single genetic intervention has recapitulated the full effects of DR, and no unified system is known for different DR regimens. Here we obtain temporally resolved transcriptomes during calorie restriction and intermittent fasting in Caenorhabditis elegans and find that early and late responses involve metabolism and cell cycle/DNA damage, respectively. We uncover three network modules of DR regulators by their target specificity. By genetic manipulations of nodes representing discrete modules, we induce transcriptomes that progressively resemble DR as multiple nodes are perturbed. Targeting all three nodes simultaneously results in extrem

SUBMITTER: Hou L 

PROVIDER: S-EPMC5110149 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature