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. 2015 Aug;37(4):9814.
doi: 10.1007/s11357-015-9814-9. Epub 2015 Jul 19.

Transcriptomic and Epigenetic Analyses Reveal a Gender Difference in Aging-Associated Inflammation: The Vitality 90+ Study

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Free PMC article

Transcriptomic and Epigenetic Analyses Reveal a Gender Difference in Aging-Associated Inflammation: The Vitality 90+ Study

T Nevalainen et al. Age (Dordr). .
Free PMC article

Abstract

Aging is associated with a pro-inflammatory state, often referred to as inflammaging. The origin of the pro-inflammatory mediators and their role in the pathogenesis of the aging-associated diseases remain poorly understood. As aging is also associated with profound changes in the transcriptomic and epigenetic (e.g., DNA methylation) profiles of cells in the peripheral blood, we analyzed the correlation of these profiles with inflammaging using the "classical" marker interleukin-6 as an indicator. The analysis of the whole-genome peripheral blood mononuclear cell (PBMC) gene expression revealed 62 transcripts with expression levels that significantly correlated with the plasma interleukin-6 (IL-6) levels in men, whereas no correlations were observed in women. The Gene Ontology analysis of plasma IL-6-associated transcripts in men revealed processes that were linked to the inflammatory response. Additionally, an Ingenuity Pathway Analysis (IPA) pathway analysis identified Tec kinase signaling as an affected pathway and upstream regulator analysis predicted the activation of IL-10 transcript. DNA methylation was assessed using a HumanMethylation450 array. Seven genes with expression profiles that were associated with the plasma IL-6 levels in men were found to harbor CpG sites with methylation levels that were also associated with the IL-6 levels. Among these genes were IL1RN, CREB5, and FAIM3, which mapped to a network of inflammatory response genes. According to our results, inflammaging is manifested differently at the genomic level in nonagenarian men and women. Part of this difference seems to be of epigenetic origin. These differences point to the genomic regulation of inflammatory response and suggest that the gender-specific immune system dimorphism in older individuals could be accounted for, in part, by DNA methylation.

Figures

Fig. 1
Fig. 1
Inverse correlations were observed between the expression levels of the three genes and the CpG sites that resided in their corresponding gene bodies. X-axis visualizes the relative gene expression level of the gene while the Y-axis depicts the β-value, corresponding to the level of DNA methylation
Fig. 2
Fig. 2
IPA network categorized as inflammatory response, cell-to-cell signaling and interaction, and cellular movement. Three genes of this network, IL1RN, CREB5, and FAIM3, were identified as associated with plasma IL-6 levels in both epigenetic and transcriptomic analyses in nonagenarian men. The figure shows interactions that these genes have within the network

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