Background: Disrupted diurnal rhythms cause accelerated aging and an increased incidence in age-related disease and morbidity. The circadian clock governs cell physiology and metabolism by controlling transcription and chromatin. The goal of this study is to further understand the mechanism of age-related changes to circadian chromatin with a focus on facultative heterochromatin and diurnal non-coding RNAs.
Results: We performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups to examine the connection between age-related changes to circadian transcription and heterochromatin in neuronal tissue. Our analysis focused on uncovering the relationships between long non-coding RNA (lncRNA) and age-related changes to histone H3 lysine 9 tri-methylation (H3K9me3), in part because the Period (Per) complex can direct facultative heterochromatin and models of aging suggest age-related changes to heterochromatin and DNA methylation. Our results reveal that lncRNAs and circadian output change dramatically with age, but the core clock genes remain rhythmic. Age-related changes in clock-controlled gene (ccg) expression indicate there are age-dependent circadian output that change from anabolic to catabolic processes during aging. In addition, there are diurnal and age-related changes in H3K9me3 that coincide with changes in transcription.
Conclusions: The data suggest a model where some age-related changes in diurnal expression are partially attributed to age-related alterations to rhythmic facultative heterochromatin. The changes in heterochromatin are potentially mediated by changes in diurnal lncRNA creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.
Keywords: Aging; Circadian rhythm; Diurnal; Heterochromatin; Histone H3 lysine 9 methylation; Long non-coding RNA.