PMID- 17874999 OWN - NLM STAT- MEDLINE DCOM- 20071207 LR - 20211203 IS - 1474-9718 (Print) IS - 1474-9718 (Linking) VI - 6 IP - 5 DP - 2007 Oct TI - Transcriptional response to aging and caloric restriction in heart and adipose tissue. PG - 673-88 AB - 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. FAU - Linford, Nancy J AU - Linford NJ AD - Department of Pathology, University of Washington, Seattle, WA 98195, USA. FAU - Beyer, Richard P AU - Beyer RP FAU - Gollahon, Katherine AU - Gollahon K FAU - Krajcik, Rozlyn A AU - Krajcik RA FAU - Malloy, Virginia L AU - Malloy VL FAU - Demas, Vasiliki AU - Demas V FAU - Burmer, Glenna C AU - Burmer GC FAU - Rabinovitch, Peter S AU - Rabinovitch PS LA - eng GR - F32 AG021827/AG/NIA NIH HHS/United States GR - 4 R44 AG16550/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Aging Cell JT - Aging cell JID - 101130839 RN - 0 (PPAR gamma) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adipogenesis MH - Adipose Tissue, White/*metabolism MH - Aging/*genetics MH - Animals MH - *Caloric Restriction MH - Gene Expression Profiling MH - *Gene Expression Regulation MH - Male MH - Myocardium/*metabolism MH - Oligonucleotide Array Sequence Analysis MH - PPAR gamma/genetics/metabolism MH - Protein Kinases/genetics MH - Rats MH - Rats, Inbred F344 MH - Reverse Transcriptase Polymerase Chain Reaction MH - TOR Serine-Threonine Kinases MH - *Transcription, Genetic EDAT- 2007/09/19 09:00 MHDA- 2007/12/08 09:00 CRDT- 2007/09/19 09:00 PHST- 2007/09/19 09:00 [pubmed] PHST- 2007/12/08 09:00 [medline] PHST- 2007/09/19 09:00 [entrez] AID - ACE319 [pii] AID - 10.1111/j.1474-9726.2007.00319.x [doi] PST - ppublish SO - Aging Cell. 2007 Oct;6(5):673-88. doi: 10.1111/j.1474-9726.2007.00319.x.