Transcriptional response to aging and caloric restriction in heart and adipose tissue

Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Aging Cell (Impact Factor: 6.34). 11/2007; 6(5):673-88. DOI: 10.1111/j.1474-9726.2007.00319.x
Source: PubMed


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 white adipose tissue (WAT) of Fischer 344 (F344) male rats using Affymetrix RAE 230 arrays and validated by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on 18 genes. As expected, age had a substantial effect on transcription on both tissues, although only 21% of cardiac age-associated genes were also altered in WAT. Gene set enrichment analysis revealed coordinated small magnitude changes in ribosomal, proteasomal, and mitochondrial genes with similarities in aging between heart and WAT. CR had very different effects on these two tissues at the transcriptional level. In heart, very few age-associated expression changes were affected by CR, while in WAT, CR suppressed a substantial subset of the age-associated changes. Genes unaltered by aging but altered by CR were identified in WAT but not heart. Most interestingly, we identified a gene expression signature associated with mammalian target of rapamycin (mTOR) activity that was down-regulated with age but preserved by CR in both WAT and heart. In addition, lipid metabolism genes, particularly those associated with peroxisome proliferator-activated receptor gamma (PPARgamma)-mediated adipogenesis were reduced with age but preserved with CR in WAT. These results highlight tissue-specific differences in the gene expression response to CR and support a role for CR-mediated preservation of mTOR activity and adipogenesis in aging WAT.

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Available from: Virginia L Malloy, Nov 21, 2014
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    • "We proceeded to also analyze mTORC1 signaling in white adipose tissue and heart, tissues in which mTOR signaling has been predicted to decrease with age based on transcriptional profiling (Linford et al., 2007). Surprisingly, we observed a massive increase in S6 phosphorylation in adipose tissue, with phosphorylation of S6 increasing three-fold in Middle-aged and Old males and approximately six-fold in Middle-aged and Old females (Fig. 1C). "
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