PMID- 12419851 OWN - NLM STAT- MEDLINE DCOM- 20030115 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 99 IP - 23 DP - 2002 Nov 12 TI - Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. PG - 14988-93 AB - To provide a global analysis of gene expression in the aging heart, we monitored the expression of 9,977 genes simultaneously in 5- and 30-month-old male B6C3F(1) mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterations consistent with a metabolic shift from fatty acid to carbohydrate metabolism, increased expression of extracellular matrix genes, and reduced protein synthesis. Caloric restriction (CR) started at 14 months of age resulted in a 19% global inhibition of age-related changes in gene expression. Interestingly, CR also resulted in alterations in gene expression consistent with preserved fatty acid metabolism, reduced endogenous DNA damage, decreased innate immune activity, apoptosis modulation, and a marked cytoskeletal reorganization. These observations provide evidence that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming. FAU - Lee, Cheol-Koo AU - Lee CK AD - Molecular and Environmental Toxicology Center, Madison, WI 53706, USA. FAU - Allison, David B AU - Allison DB FAU - Brand, Jaap AU - Brand J FAU - Weindruch, Richard AU - Weindruch R FAU - Prolla, Tomas A AU - Prolla TA LA - eng GR - R01 AG018922/AG/NIA NIH HHS/United States GR - R01AG18922/AG/NIA NIH HHS/United States GR - U24DK058776/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20021105 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Enzymes) RN - 0 (Proteins) SB - IM MH - Aging/*genetics MH - Algorithms MH - Animals MH - *Diet, Reducing MH - Enzymes/genetics MH - Gene Expression Regulation, Developmental/*genetics MH - Heart/*growth & development MH - Male MH - Mice MH - Mice, Inbred Strains MH - Models, Genetic MH - Nucleic Acid Hybridization MH - Proteins/genetics MH - *Transcription, Genetic PMC - PMC137532 EDAT- 2002/11/07 04:00 MHDA- 2003/01/16 04:00 PMCR- 2003/05/12 CRDT- 2002/11/07 04:00 PHST- 2002/11/07 04:00 [pubmed] PHST- 2003/01/16 04:00 [medline] PHST- 2002/11/07 04:00 [entrez] PHST- 2003/05/12 00:00 [pmc-release] AID - 232308999 [pii] AID - pq2302014988 [pii] AID - 10.1073/pnas.232308999 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14988-93. doi: 10.1073/pnas.232308999. Epub 2002 Nov 5.