title: Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver.
abstract: Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
authors.forename: Wilson C
authors.initials: WC
authors.lastname: Fok
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gelfond
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Doderer
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Martin
authors.initials: M
authors.lastname: Javors
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Pérez
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D055442:Metabolome / Q000187:drug effects* / Q000235:genetics; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics
chemical_list: D020123:Sirolimus
keywords: dietary restriction; metabolome; rapamycin; transcriptome