Distinct epigenomes in CD4+ T cells of newborns, middle-ages and centenarians

Abstract

Age-related variations in genes and microRNAs expression and DNA methylation have been reported respectively; however, their interactions during aging are unclear. We therefore investigated alterations in the transcriptomes, miRNAomes and DNA methylomes in the same CD4+T cells from newborn (NB), middle-aged (MA) and long-lived (LL) individuals to elucidate the molecular changes and their interactions. A total 659 genes showed significantly expression changes across NB, MA and LL individuals, in which we identified four age-related co-expression modules with three hub networks of co-expressed genes and non-coding RNAs. Moreover, we identified 9835 differentially methylated regions (DMRs) including 7015 hypermethylated and 2820 hypomethylated DMRs in the NB compared with the MA, and 12,362 DMRs including 4809 hypermethylated and 7553 hypomethylated DMRs in the MA compared with the LL. The integrated analysis revealed a potential relationship between genes transcription and DNA methylation for many age- or immune-related genes, suggesting that DNA methylation-dependent transcription regulation is involved in development and functions of T cells during aging. Our results reveals age-related transcription and methylation changes and their interactions in human T cells from the cradle to the grave. Longitudinal work is required to establish the relationship between identified age-associated genes/DNA methylation and T cells aging phenotypes.

Detailed analysis of adenosine A2a receptor (ADORA2A) and CD73 (5′-nucleotidase, ecto,NT5E) methylation and gene expression in head and neck squamous cell carcinoma patients

“…CD4 C T cells and CD14 C monocytes. 33,34 Such age-associated methylation changes frequently affect genes involved in immune processes which are predominantly demethylated with increasing age. [35][36][37] Figure 5.…”

Ageing and epigenetics: linking neurodevelopmental and neurodegenerative disorders

“…22 It may be, then, that DNA methylation of specific sites drives health behaviours rather than those behaviours modulating methylation patterns. 27 However, relatively few microRNAs are likely to be involved across different tissue types related to coreageing mechanisms, as opposed to tissue-specific types. However, DNA methylation profiles associated with these are less explored, though there is limited data linking increased methylation with age-related cataracts and coronary artery disease via oxidative stress, 23,24 and for childhood socio-economic status being associated with individual DNA methylation differences related to inflammation genes.…”

“…26 Similarly, there are strong functional network links between DNA methylation and microRNAs impacting on immune function over the lifespan. 27 However, relatively few microRNAs are likely to be involved across different tissue types related to coreageing mechanisms, as opposed to tissue-specific types. 28 Nevertheless, this is an area of considerable therapeutic interest in neurodegenerative diseases, particularly since the announcement of preliminary results from a phase II trial of an antisense oligonucleotide administered intrathecally that showed reduced huntingtin protein in Huntington disease.…”

Molecular Basis of Neurodegeneration: Lessons from Alzheimer’s and Parkinson’s Diseases

“…While toll-like receptors (TLRs), which are activated by different subcellular molecular components (damage-associated molecular patterns, DAMPs), signal through NFκb to release several pro-inflammatory cytokines, leading to activation of the immune response, the very same NFκb constitutes an oxidative stress sensor, connecting the increased levels of ROS/RNS with activation of the inflammatory cascade [20,21]. Additionally, it must be considered that immunocompetence is usually compromised in aged individuals, and several authors have shown that this decay is closely linked to the altered epigenetic control of several immune-related genes [22][23][24]. Altogether, this evidence suggests that the difference between "normal" and pathological ageing lies in the subtle equilibrium of different homeostatic The delicate balance that sustains healthy ageing can be broken under several conditions.…”