Altered gene expression pattern indicates the differential regulation of the immune response system as an important factor in cardiac aging

Abstract

Numerous changes occur in the old myocardium which finally cause lower cardiac output and, therefore, circulatory dysfunction. In order to identify an age-related gene expression pattern, we analyzed left ventricular myocardium of adult (6 months) and old (24 months) mice by use of whole genome expression arrays. About 2.3% of genes expressed above the median value of all genes were differentially expressed in old hearts. Nearly all of them were upregulated. After application of defined exclusion criteria, 98 genes were selected for a more detailed analysis. About one third of the 98 genes codes for factors involved in the immune reaction, such as chemokines (CCLs 6, 8, 9), proteins of the S100 family (S100s 4, 8, 9, 10, 11), complement components (C1qa, C1qb, C1qc, C3, C4b), bacteria/virus-induced genes (lysozyme 1/2, interferon-activated genes), and pro-inflammatory caspases (Casp1, Casp4, Casp12). Predominantly, genes coding for factors of the immune reaction were simultaneously upregulated in the kidneys and lungs of old mice, thereby emphasizing the pivotal role of immune cells in tissue aging. In conclusion, myocardial aging is mainly associated with an altered expression pattern of molecules involved in the immune reaction.

Keywords: Age; Gene expression; Mouse; Myocardium.