Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

作者：Cheol‐Koo Lee, David B. Allison, Jaap Brand, Richard Weindruch, Tomas A. Prolla · 发表于：Proceedings of the National Academy of Sciences · 年份：2002 · DOI：10.1073/pnas.232308999 · 被引用次数：320 · 研究领域：Adipose Tissue and Metabolism、Cardiac Fibrosis and Remodeling、Genetics, Aging, and Longevity in Model Organisms

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.