Background: Altered DNA methylation patterns represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Several studies have described global and complex age-related methylation changes, but their structural and functional significance has remained largely unclear. Results: We have used transcriptome sequencing to characterize age-related gene expression changes in the human epidermis. The results revealed a significant set of 75 differentially expressed genes with a strong functional relationship to skin homeostasis. We then used whole-genome bisulfite sequencing to identify age-related methylation changes at single-base resolution. Data analysis revealed no global aberrations, but rather highly localized methylation changes, particularly in promoter and enhancer regions that were associated with altered transcriptional activity. Conclusions: Our results suggest that the core developmental program of human skin is stably maintained through the aging process and that aging is associated with a limited destabilization of the epigenome at gene regulatory elements.
Bibliographical noteFunding Information:
We thank André Leischwitz and the DKFZ Genomics and Proteomics Core Facility for sequencing services. We also thank Franz Stäb and Horst Wenck for their support. This work was funded by the BMBF-GerontoSys program through the project AGENET (FKZ0315898).
- DNA methylation
- Methylome sequencing
- Transcriptome sequencing