Transcriptomic and epigenetic analyses reveal a gender difference in aging-associated inflammation: the Vitality 90+...

Area of Science:

• Gerontology
• Immunology
• Genomics
• Epigenetics

Background:

• Aging is linked to a pro-inflammatory state known as inflammaging, but its origins and role in age-related diseases are unclear.
• Significant transcriptomic and epigenetic changes occur during aging, potentially influencing inflammaging.
• Interleukin-6 (IL-6) is a key inflammatory marker used to study inflammaging.

Purpose of the Study:

• To investigate the correlation between genomic profiles (gene expression and DNA methylation) and inflammaging, using IL-6 as a marker.
• To explore potential gender-specific differences in the genomic regulation of inflammaging.

Main Methods:

• Analysis of whole-genome gene expression in peripheral blood mononuclear cells (PBMCs).
• Correlation analysis of gene expression and plasma IL-6 levels in nonagenarians.
• DNA methylation analysis using the HumanMethylation450 array.
• Gene Ontology and Ingenuity Pathway Analysis (IPA) for pathway and upstream regulator identification.

Main Results:

• In men, 62 transcripts in PBMCs significantly correlated with plasma IL-6 levels, linked to inflammatory response pathways.
• No significant correlations were found between gene expression and IL-6 levels in women.
• Tec kinase signaling was identified as an affected pathway, with IL-10 predicted as an upstream regulator in men.
• Seven genes showed associations between both expression and DNA methylation levels with plasma IL-6 in men, including IL1RN, CREB5, and FAIM3.

Conclusions:

• Inflammaging manifests differently at the genomic level in older men and women.
• Epigenetic modifications, particularly DNA methylation, appear to contribute to these gender-specific differences.
• These findings highlight the role of genomic regulation in inflammatory responses and suggest DNA methylation may underlie gender-specific immune dimorphism in aging.