Abstract

BackgroundThe microRNAs have been implicated in the process of cardiac development, cardiac hypertrophy, and heart failure. However, the impact of adult aging on cardiac expression of miRNA clusters, as well as both miRNA guide (miR) and passenger (miR*) strands has not been well established.Methods/ResultsWe explored the expression profile of both miR and miR* in the hearts of young adult versus old mice. We found that 65 miRNAs were differentially expressed in the old versus young adult hearts; approximately half of them were clustered miRNAs that were distributed in 11 miRNA clusters. Each miRNA cluster contained from 2 to as many as 71 miRNA genes. The majority of the clusters displayed similar expression, with most cluster members within a cluster being either increased or decreased together, suggesting that most clusters are likely to be regulated by a common signaling mechanism and that the combined expression of multiple miRNA genes in a cluster could pose an impact on a broad range of targets during aging. We also found age-related changes in the expression of miR*s. The expression of both miR and miR* correlated with that of pri-miRNA transcript over the time course from development and maturation through adult aging. Age-related changes in the expression of Ago1 and Ago2 proteins in the heart were also observed. Transfection assay revealed that both Ago1 and Ago2 synergistically induced miR-21 and miR-21* when the mir-21 plasmid was co-transfected with either.ConclusionThe data revealed age-related changes in the expression of pri-miRNA transcript, Argonaut proteins and both miR and miR* strands. The major changes occurred later in life, from middle to old age. It is likely that the expression of miR and miR* is regulated by both pri-miRNA transcription as well as Ago1 and Ago2 proteins during adult aging.

Highlights

  • Adult aging is a complex biological process associated with a progressive decline in the physiological and biochemical performance of individual tissues and organs, leading to increased susceptibility to age-related disease and functional senescence [1,2,3,4]

  • It is likely that the expression of miRNA guide (miR) and miR* is regulated by both pri-miRNA transcription as well as Ago1 and Ago2 proteins during adult aging

  • It has been reported that microRNA expression was altered in cardiac hypertrophy, congestive heart failure and in senescent cells [27,28,29,30,31]

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Summary

Introduction

Adult aging is a complex biological process associated with a progressive decline in the physiological and biochemical performance of individual tissues and organs, leading to increased susceptibility to age-related disease and functional senescence [1,2,3,4]. The functional changes observed in the older heart are usually associated with morphological changes that occur during the normal aging process, which is characterized by a loss of myocytes with subsequent hypertrophy of the remaining viable myocytes, and proliferation of cardiac fibroblasts. The functional and morphological changes in the older heart are accompanied by changes in cardiac gene expression, which include a-MHC, b-MHC, ANF, SERCA2 etc. Recent studies suggest that microRNAs (miRNAs) may play a role in the regulation of gene expression in the aging process [11,12,13]. The impact of adult aging on cardiac expression of miRNA clusters, as well as both miRNA guide (miR) and passenger (miR*) strands has not been well established

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