Project description:Various risk factors in aging contribute to the pathogenesis of frailty. Epigenetic changes are among the factors that influence gene expression. It plays a role in regulating the immune system during aging, especially DNA methylation. DNA methylation profiles in the elderly have been widely studied. However, the differences in methylation patterns between robust and frail aging populations remain underexplored. A total of 32 subjects were recruited (age ≥ 65 years old) , consisting of 16 as the frail group and 16 as the robust group. For further methylation sequencing, only one robust subject and four frail subjects were selected. The selection of these individuals was based on their TNF-α concentrations, representing one subject with the lowest and four with the highest TNF-α levels. In this study, we identified an association between altered DNA methylation patterns, mRNA expression levels, and inflammatory conditions in frail elderly. The differential expression of certain genes is likely influenced by differences in methylation level between the frail and robust groups. In overall methylation, the differential of 5mC was slightly significant (p=0.06), while 5hmC was not significantly different (p=0.53). We aim to investigate these differences to gain a deeper understanding of the pathogenesis of frailty in some specific genes.
Project description:Illumina Infinium EPIC HumanMethylation BeadChip data from saliva DNA samples from a healthy elderly cohort with individuals in the age range 70-95 in Southwest Sweden. The cohort was stratified into study groups based on participants´answers to a questionnaire of different lifestyle factors including vitamin supplementations, smoking and drinking habits, physical activity (per year), sun exposure and eating habits. Vitamin D intake was evaluated from the vitamin D supplementation (alone or in a multivitamin complex), dietary vitamin D intake (fish and seafood frequency) and vitamin D synthesis in the skin (sunlight exposure and use of sunscreen). Differential methylation analysis was performed for all the study groups and the combination of different factors with vitamin D supplementation. Gender, age, smoking and alcohol (SD and frequency) were used as covariates in the analyses. Only the study groups referred to the conclusions of the study are shown.
Project description:DNA methylation levels in whole blood measured over a ten years follow up in an elderly birth cohort of 86 samples For each sample, whole blood was drawn in year 1997 and in year 2007 Follow-up design: Same participant was measured over time in 1997 and 2007
Project description:The data contains Illumina 450k/EPIC array methylation files from 104 patients of the NOA-08 study comparing temozolomide alone vs. radiotherapy in elderly patients with glioblastoma
Project description:Frailty is an intermediate status of human ageing process, associated with decompensated homeostasis and death. The immune phenotype of frailty and its underlying cellular and molecular processes remain poorly understood. Here we profiled 114,467 immune cells from cord blood, young adults, healthy and frail elderly using single-cell RNA and TCR V(D)J sequencing. An age-dependent accumulation of cell heterogeneity and transcriptome variability in defined immune cell types was observed. With the specific expression of gene sets, characteristic transcription factors were identified in given immune cell types of certain age group. Trajectory analysis revealed cells from non-frail and frail elderly often fall into distinct trajectories, despite similar chronological age. Numerous TCR clonotypes were shared among T cell subtypes in aged and frail samples, indicating differential pluripotency and resilience capability of aged T cells. Finally, a frailty-specific monocyte subset was identified with exclusively high expression of lncRNAs NEAT1 and MALAT1. Our results discover human frailty-specific immune cell characteristics based on the comprehensive dimensions in immune landscape of ageing and frailty.