Project description:Altered DNA methylation patterns represent an attractive mechanism for the phenotypic changes associated with human aging. Several studies have described age-related methylation changes to various extents, but their functional significance has remained largely unclear. We have now used an integrated methylome and transcriptome sequencing approach to characterize age-related methylation changes in the human epidermis and to analyze their impact on gene expression. Our results show limited and localized methylation differences between young and old methylomes at single-base resolution. Similarly, the comparison of transcriptomes from young and old samples revealed a highly defined set of differentially expressed genes with functional annotations in skin homeostasis. Further data analysis showed a robust correlation between age-related promoter hypermethylation and gene silencing, particularly at promoters that were pre-marked with stem cell-specific chromatin features. In addition, we also observed age-related methylation changes at transcription factor binding sites, with a significant enrichment of stem cell regulatory networks. Our results provide a high-resolution analysis of age-related methylation changes and suggest that they result in highly defined alterations in the transcriptional programme of the human epidermis. Interestingly, several of our findings can be interpreted to reflect epigenetic changes in aging stem cells, thus supporting a critical role of stem cells in human aging. Whole genome methylation analysis of H. sapiens. Two samples were analyzed, one sample containing DNA from young, one sample containing DNA from old human skin.
Project description:Altered DNA methylation patterns represent an attractive mechanism for the phenotypic changes associated with human aging. Several studies have described age-related methylation changes to various extents, but their functional significance has remained largely unclear. We have now used an integrated methylome and transcriptome sequencing approach to characterize age-related methylation changes in the human epidermis and to analyze their impact on gene expression. Our results show limited and localized methylation differences between young and old methylomes at single-base resolution. Similarly, the comparison of transcriptomes from young and old samples revealed a highly defined set of differentially expressed genes with functional annotations in skin homeostasis. Further data analysis showed a robust correlation between age-related promoter hypermethylation and gene silencing, particularly at promoters that were pre-marked with stem cell-specific chromatin features. In addition, we also observed age-related methylation changes at transcription factor binding sites, with a significant enrichment of stem cell regulatory networks. Our results provide a high-resolution analysis of age-related methylation changes and suggest that they result in highly defined alterations in the transcriptional programme of the human epidermis. Interestingly, several of our findings can be interpreted to reflect epigenetic changes in aging stem cells, thus supporting a critical role of stem cells in human aging. Whole transcriptome analysis of H. sapiens. Two samples were analyzed, one sample containing RNA from young, one sample containing RNA from old human skin.
Project description:Altered DNA methylation patterns represent an attractive mechanism for the phenotypic changes associated with human aging. Several studies have described age-related methylation changes to various extents, but their functional significance has remained largely unclear. We have now used an integrated methylome and transcriptome sequencing approach to characterize age-related methylation changes in the human epidermis and to analyze their impact on gene expression. Our results show limited and localized methylation differences between young and old methylomes at single-base resolution. Similarly, the comparison of transcriptomes from young and old samples revealed a highly defined set of differentially expressed genes with functional annotations in skin homeostasis. Further data analysis showed a robust correlation between age-related promoter hypermethylation and gene silencing, particularly at promoters that were pre-marked with stem cell-specific chromatin features. In addition, we also observed age-related methylation changes at transcription factor binding sites, with a significant enrichment of stem cell regulatory networks. Our results provide a high-resolution analysis of age-related methylation changes and suggest that they result in highly defined alterations in the transcriptional programme of the human epidermis. Interestingly, several of our findings can be interpreted to reflect epigenetic changes in aging stem cells, thus supporting a critical role of stem cells in human aging.
Project description:Altered DNA methylation patterns represent an attractive mechanism for the phenotypic changes associated with human aging. Several studies have described age-related methylation changes to various extents, but their functional significance has remained largely unclear. We have now used an integrated methylome and transcriptome sequencing approach to characterize age-related methylation changes in the human epidermis and to analyze their impact on gene expression. Our results show limited and localized methylation differences between young and old methylomes at single-base resolution. Similarly, the comparison of transcriptomes from young and old samples revealed a highly defined set of differentially expressed genes with functional annotations in skin homeostasis. Further data analysis showed a robust correlation between age-related promoter hypermethylation and gene silencing, particularly at promoters that were pre-marked with stem cell-specific chromatin features. In addition, we also observed age-related methylation changes at transcription factor binding sites, with a significant enrichment of stem cell regulatory networks. Our results provide a high-resolution analysis of age-related methylation changes and suggest that they result in highly defined alterations in the transcriptional programme of the human epidermis. Interestingly, several of our findings can be interpreted to reflect epigenetic changes in aging stem cells, thus supporting a critical role of stem cells in human aging.
2013-12-20 | GSE46486 | GEO
Project description:Association Between Early Life DNA Methylation Patterns with Age-Related Transcriptional Changes
Project description:Epigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age-related changes in DNA methylation at the genome scale have been termed epigenetic drift, but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age-related epigenetic changes because of its substantial cell-type homogeneity and its well-known age-related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N=108) using array-based profiling of 450,000 methylation marks in various age groups. Data analysis confirmed that age-related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovers an age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome. This data set contains data from transcription profiling by array of human epidermis samples. The results of methylation profiling are provided in the ArrayExpress experiment E-MTAB-4385.
Project description:Background: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach. Results: We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age. Conclusions: This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference between the two age periods.
Project description:Epigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age-related changes in DNA methylation at the genome scale have been termed epigenetic drift, but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age-related epigenetic changes because of its substantial cell-type homogeneity and its well-known age-related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N=108) using array-based profiling of 450,000 methylation marks in various age groups. Data analysis confirmed that age-related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovers an age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome. This data set contains data from methylation profiling by array of human epidermis samples. The results of transcription profiling by array are provided in the ArrayExpress experiment E-MTAB-4382.