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Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver

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...

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Autores principales: Fok, Wilson C, Bokov, Alex, Gelfond, Jonathan, Yu, Zhen, Zhang, Yiqiang, Doderer, Mark, Chen, Yidong, Javors, Martin, Wood, William H, Zhang, Yongqing, Becker, Kevin G, Richardson, Arlan, Pérez, Viviana I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989927/
https://www.ncbi.nlm.nih.gov/pubmed/24304444
http://dx.doi.org/10.1111/acel.12175
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author Fok, Wilson C
Bokov, Alex
Gelfond, Jonathan
Yu, Zhen
Zhang, Yiqiang
Doderer, Mark
Chen, Yidong
Javors, Martin
Wood, William H
Zhang, Yongqing
Becker, Kevin G
Richardson, Arlan
Pérez, Viviana I
author_facet Fok, Wilson C
Bokov, Alex
Gelfond, Jonathan
Yu, Zhen
Zhang, Yiqiang
Doderer, Mark
Chen, Yidong
Javors, Martin
Wood, William H
Zhang, Yongqing
Becker, Kevin G
Richardson, Arlan
Pérez, Viviana I
author_sort Fok, Wilson C
collection PubMed
description 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.
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spelling pubmed-39899272015-02-19 Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver Fok, Wilson C Bokov, Alex Gelfond, Jonathan Yu, Zhen Zhang, Yiqiang Doderer, Mark Chen, Yidong Javors, Martin Wood, William H Zhang, Yongqing Becker, Kevin G Richardson, Arlan Pérez, Viviana I Aging Cell Original Articles 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. BlackWell Publishing Ltd 2014-04 2013-12-05 /pmc/articles/PMC3989927/ /pubmed/24304444 http://dx.doi.org/10.1111/acel.12175 Text en © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Fok, Wilson C
Bokov, Alex
Gelfond, Jonathan
Yu, Zhen
Zhang, Yiqiang
Doderer, Mark
Chen, Yidong
Javors, Martin
Wood, William H
Zhang, Yongqing
Becker, Kevin G
Richardson, Arlan
Pérez, Viviana I
Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
title Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
title_full Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
title_fullStr Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
title_full_unstemmed Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
title_short Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
title_sort combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989927/
https://www.ncbi.nlm.nih.gov/pubmed/24304444
http://dx.doi.org/10.1111/acel.12175
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