Transcriptional Profiles Associated with Aging and Middle Age-Onset Caloric Restriction in Mouse Hearts

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 B6C3F1mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterat...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 99; no. 23; pp. 14988 - 14993
Main Authors Lee, Cheol-Koo, Allison, David B., Brand, Jaap, Weindruch, Richard, Prolla, Tomas A.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 12.11.2002
National Acad Sciences
Subjects
Actins
Aging
Aging - genetics
Algorithms
Animals
Apoptosis
Biological Sciences
Collagens
Diet, Reducing
Enzymes
Enzymes - genetics
Fatty acids
Gene expression
Gene Expression Regulation, Developmental - genetics
Genes
Heart
Heart - growth & development
Lipid metabolism
Male
Mice
Mice, Inbred Strains
Models, Genetic
Nucleic Acid Hybridization
P values
Proteins - genetics
Rodents
Transcription, Genetic
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Summary: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 B6C3F1mice 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.
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To whom correspondence may be addressed. E-mail: taprolla@facstaff.wisc.edu or rhweindr@wisc.edu.
Edited by John W. Suttie, University of Wisconsin, Madison, WI, and approved August 28, 2002
This paper was submitted directly (Track II) to the PNAS office.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.232308999