PMID- 29514073 OWN - NLM STAT- MEDLINE DCOM- 20190820 LR - 20190820 IS - 1932-7420 (Electronic) IS - 1550-4131 (Print) IS - 1550-4131 (Linking) VI - 27 IP - 3 DP - 2018 Mar 6 TI - Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys. PG - 677-688.e5 LID - S1550-4131(18)30066-4 [pii] LID - 10.1016/j.cmet.2018.01.014 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Rhoads, Timothy W AU - Rhoads TW AD - Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA. FAU - Burhans, Maggie S AU - Burhans MS AD - Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA. FAU - Chen, Vincent B AU - Chen VB AD - National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Hutchins, Paul D AU - Hutchins PD AD - Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Rush, Matthew J P AU - Rush MJP AD - Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Clark, Josef P AU - Clark JP AD - Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA. FAU - Stark, Jaime L AU - Stark JL AD - National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - McIlwain, Sean J AU - McIlwain SJ AD - Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53792, USA. FAU - Eghbalnia, Hamid R AU - Eghbalnia HR AD - National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Pavelec, Derek M AU - Pavelec DM AD - University of Wisconsin Biotechnology Center, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Ong, Irene M AU - Ong IM AD - Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53792, USA. FAU - Denu, John M AU - Denu JM AD - Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA. FAU - Markley, John L AU - Markley JL AD - National Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. FAU - Coon, Joshua J AU - Coon JJ AD - Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA. FAU - Colman, Ricki J AU - Colman RJ AD - Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA. FAU - Anderson, Rozalyn M AU - Anderson RM AD - Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA; Geriatric Research, Education, and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA. Electronic address: rozalyn.anderson@wisc.edu. LA - eng GR - P51 RR000167/RR/NCRR NIH HHS/United States GR - T15 LM007359/LM/NLM NIH HHS/United States GR - R35 GM118110/GM/NIGMS NIH HHS/United States GR - R01 AG040178/AG/NIA NIH HHS/United States GR - T32 AG000213/AG/NIA NIH HHS/United States GR - R56 AG047358/AG/NIA NIH HHS/United States GR - P41 GM108538/GM/NIGMS NIH HHS/United States GR - P51 OD011106/OD/NIH HHS/United States GR - P41 GM103399/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell Metab JT - Cell metabolism JID - 101233170 RN - 63231-63-0 (RNA) MH - Aging/metabolism MH - Animals MH - *Caloric Restriction MH - Gene Expression MH - Liver/*metabolism MH - Macaca mulatta MH - Male MH - RNA/*metabolism MH - *RNA Processing, Post-Transcriptional PMC - PMC5844481 MID - NIHMS939797 OTO - NOTNLM OT - RNA processing OT - aging OT - caloric restriction OT - lipid metabolism OT - metabolism OT - rhesus macaque COIS- DECLARATION OF INTERESTS The authors declare no competing interests. EDAT- 2018/03/08 06:00 MHDA- 2019/08/21 06:00 PMCR- 2019/03/06 CRDT- 2018/03/08 06:00 PHST- 2017/05/23 00:00 [received] PHST- 2017/09/29 00:00 [revised] PHST- 2018/01/28 00:00 [accepted] PHST- 2018/03/08 06:00 [entrez] PHST- 2018/03/08 06:00 [pubmed] PHST- 2019/08/21 06:00 [medline] PHST- 2019/03/06 00:00 [pmc-release] AID - S1550-4131(18)30066-4 [pii] AID - 10.1016/j.cmet.2018.01.014 [doi] PST - ppublish SO - Cell Metab. 2018 Mar 6;27(3):677-688.e5. doi: 10.1016/j.cmet.2018.01.014.