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Mech Ageing Dev. 2014 Sep;140:23-9. doi: 10.1016/j.mad.2014.07.004. Epub 2014 Jul 27.

Short-term rapamycin treatment in mice has few effects on the transcriptome of white adipose tissue compared to dietary restriction.

Author information

1
Department of Internal Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, MO 63110, USA.
2
Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
3
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
4
Linus Pauling Institute, Corvallis, OR, USA.
5
Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
6
Department of Internal Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, MO 63110, USA; Oklahoma City VA Medical Center, Oklahoma City, OK 73104, USA.
7
Oklahoma City VA Medical Center, Oklahoma City, OK 73104, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA. Electronic address: viviana.perez@oregonstate.edu.

Abstract

Rapamycin, a drug that has been shown to increase lifespan in mice, inhibits the target of rapamycin (TOR) pathway, a major pathway that regulates cell growth and energy status. It has been hypothesized that rapamycin and dietary restriction (DR) extend lifespan through similar mechanisms/pathways. Using microarray analysis, we compared the transcriptome of white adipose tissue from mice fed rapamycin or DR-diet for 6 months. Multidimensional scaling and heatmap analyses showed that rapamycin had essentially no effect on the transcriptome as compared to DR. For example, only six transcripts were significantly altered by rapamycin while mice fed DR showed a significant change in over 1000 transcripts. Using ingenuity pathway analysis, we found that stearate biosynthesis and circadian rhythm signaling were significantly changed by DR. Our findings showing that DR, but not rapamycin, has an effect on the transcriptome of the adipose tissue, suggesting that these two manipulations increase lifespan through different mechanisms/pathways.

KEYWORDS:

Adipose; Dietary restriction; Fat; Microarrays; Rapamycin; Transcriptome

PMID:
25075714
PMCID:
PMC4167584
DOI:
10.1016/j.mad.2014.07.004
[Indexed for MEDLINE]
Free PMC Article

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