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

Aging Cell

Wilson C. Fok¹  Alex Bokov⁶  Jonathan Gelfond²  Zhen Yu³  Yiqiang Zhang⁶  Mark Doderer⁴  Yidong Chen²  Martin Javors⁵  William H. Wood III⁷  Yongqing Zhang⁷  Kevin G. Becker⁷  Arlan Richardson¹ 

[1] Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;Linus Pauling Institute, Oregon State University, Corvallis, OR, USA;Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;National Institute on Aging, Baltimore, MD, USA

关键词: dietary restriction;    metabolome;    rapamycin;    transcriptome;   

DOI  :  10.1111/acel.12175

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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