Aging modifies splenocyte DNA methylation in response to influenza infection

Abstract

Age-related immunosenescence is associated with reduced resistance to viral infection. We investigated the epigenetic effect of age on splenocyte DNA methylation (DNAmet) response during influenza infection. Old (22 mo, n=30) and young (4 mo, n=23) male C57Bl/6 mice were intranasally infected with influenza A/Puerto Rico/8/34 virus. Genomic DNAmet was measured in spleen cells on d 0, 2, 5 or 7 post-infection (PI) by LC/MS. Immune mediators were quantified in supernatants of mitogen-stimulated splenocytes by ELISA. DNAmet reached a peak at d 2 and was significantly different from that of d 7 in old mice (5.0 vs 4.4%, p<0.01). In young mice, DNAmet reached a peak on d 5 PI without significant differences between PI days. DNAmet on d 2 was significantly higher in old compared to young mice (5.0 vs 4.6%, p<0.05), while there was no significant difference between the two age groups at the other days. On d 2 old mice had lower IL2 (p<0.05) and higher TNFα (p<0.1) production by Con A- or LPS- stimulated splenocytes, respectively. Genomic DNAmet was positively correlated with IL2 levels in old mice (p<0.05) and negatively correlated with those of TNFα (p<0.03) and IL6 (p<0.04) on d 2. These results demonstrate an age-specific change in splenocyte DNAmet that is associated with changes in immune mediators. Clinical relevance of these findings needs to be determined. Supported by Nestec Ltd. and USDA agreement #58-1950-7-707