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| Status |
Public on Oct 23, 2007 |
| Title |
Transcriptional Response to Aging and Caloric Restriction in Heart and Adipose Tissue |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Sustained caloric restriction (CR) extends lifespan in animal models but the mechanism and primary tissue target(s) have not been identified. Gene expression changes with aging and CR were examined in both heart and subcutaneous white adipose tissue (WAT) of F344 male rats using Affymetrix® RAE 230 arrays and validated by qRT-PCR on 18 genes. In heart, age- associated changes but not CR-associated changes in old. In WAT, genes were identified where the aging change is suppressed by CR (candidate markers of healthy aging) and those affected by CR but not normal aging (candidate longevity assurance genes). 10-21% of age-associated genes were regulated in common between tissues. Gene set enrichment analysis (GSEA) revealed coordinate small magnitude changes in ribosomal, proteasomal, and mitochondrial genes with similarities between heart and WAT. Further analysis revealed PPARgamma as a potential upstream regulator of altered gene expression in old CR WAT. These results demonstrate a reduced mRNA response to CR with age in heart relative to WAT. In WAT, we identified candidate CR mimetic targets and candidate markers of healthy aging. These data suggest a role for subcutaneous WAT in the effects of CR and strengthen the role for PPAR signaling in aging and CR while indicating that the effects of CR in heart can occur independent of global changes in mRNA level.
Keywords: Aging Caloric Restriction
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| Overall design |
Tissues (n=5-7 animals per group) were obtained from the NIH-NIA aging rodent tissue bank. According to supplier records, animals were housed in a specific pathogen free barrier facility under contract with BioReliance. AL animals were housed 3 per cage and CR animals were housed singly. CR (60% of AL) was initiated at 4 months of age with a switch from the NIH 31 to NIH fortified diet. F344 male rats were sacrificed at 4 months (4AL) or 28 months of age (28AL, 28CR). Animals with gross tumor pathologies were excluded from the study. All animals were euthanized by CO2 asphixiation and tissues were frozen in liquid nitrogen then stored at –80°C. Subcutaneous WAT was collected from the abdominal region. Recorded body weights differed dramatically between the 3 groups (4AL = 253±8 g, 28AL = 382±20 g, 28CR = 288±7 g) and heart weight as a fraction of body weight was not significantly different between the groups (data not shown). The apical ~1/3 of the heart was homogenized for the expression studies. Sections from the cut face were stained with haematoxylin and eosin to confirm expected aging-associated pathology changes.
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| Contributor(s) |
Beyer RP, Linford N, Rabinovitch PS |
| Citation(s) |
17874999 |
| Submission date |
Jan 11, 2007 |
| Last update date |
Sep 05, 2017 |
| Contact name |
James William MacDonald |
| E-mail(s) |
jmacdon@uw.edu
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| Organization name |
University of Washington
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| Department |
Environmental and Occupational Health Sciences
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| Street address |
4225 Roosevelt Way NE
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98105-6099 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (39)
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| Relations |
| BioProject |
PRJNA99047 |
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