Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys

Publication date: 6 March 2018
Source:Cell Metabolism, Volume 27, Issue 3
Author(s): Timothy W. Rhoads, Maggie S. Burhans, Vincent B. Chen, Paul D. Hutchins, Matthew J.P. Rush, Josef P. Clark, Jaime L. Stark, Sean J. McIlwain, Hamid R. Eghbalnia, Derek M. Pavelec, Irene M. Ong, John M. Denu, John L. Markley, Joshua J. Coon, Ricki J. Colman, Rozalyn M. Anderson
Caloric restriction (CR) extends lifespan and delays the onset of age-related disorders in diverse species. Metabolic regulatory pathways have been implicated in the mechanisms of CR, but the molecular details have not been elucidated. Here, we show that CR engages RNA processing of genes associated with a highly integrated reprogramming of hepatic metabolism. We conducted molecular profiling of liver biopsies collected from adult male rhesus monkeys (Macaca mulatta) at baseline and after 2 years on control or CR (30% restricted) diet. Quantitation of over 20,000 molecules from the hepatic transcriptome, proteome, and metabolome indicated that metabolism and RNA processing are major features of the response to CR. Predictive models identified lipid, branched-chain amino acid, and short-chain carbon metabolic pathways, with alternate transcript use for over half of the genes in the CR network. We conclude that RNA-based mechanisms are central to the CR response and integral in metabolic reprogramming.

Graphical abstract

Teaser

Rhoads et al. use multi-platform high-resolution molecular profiling to demonstrate that caloric restriction (CR) reprograms hepatic metabolism in rhesus monkeys. They identify a role for RNA processing in the mechanisms of CR and show that the CR metabolic network is subject to substantial regulation at the RNA level.


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