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

Aging Cell - Tập 13 Số 2 - Trang 311-319 - 2014
Wilson C. Fok1, Alex Bokov2,3, Jonathan Gelfond3, Zhentao Yu4, Yiqiang Zhang2,5, Mark Doderer6, Yidong Chen7,3,6, Martin A. Javors8, William H. Wood9, Yongqing Zhang9, Kevin G. Becker9, Arlan Richardson2,1,10, Viviana Pérez11,4
1Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
2Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
3Department of Epidemiology & Biostatistics The University of Texas Health Science Center at San Antonio San Antonio TX 78229 USA
4Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA.
5Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
6Greehey Children’s Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 USA
7Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
8Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
9National Institute on Aging Baltimore MD 21224 USA
10Research Service Audie Murphy VA Hospital (STVHCS) San Antonio TX 78229 USA
11Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA

Tóm tắt

SummaryRapamycin (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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Aging Cell

Tập 13 Số 2

311-319

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