Aging is associated with highly defined epigenetic changes in the human epidermis

Günter Raddatz; Sabine Hagemann; Dvir Aran; Jörn Söhle; Pranav P. Kulkarni; Lars Kaderali; Asaf Hellman; Marc Winnefeld; Frank Lyko

doi:10.1186/1756-8935-6-36

Aging is associated with highly defined epigenetic changes in the human epidermis

Günter Raddatz, Sabine Hagemann, Dvir Aran, Jörn Söhle, Pranav P. Kulkarni, Lars Kaderali, Asaf Hellman, Marc Winnefeld, Frank Lyko^*

^*Corresponding author for this work

Department of Developmental Biology and Cancer Research

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

Abstract

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.

Original language	English
Article number	36
Journal	Epigenetics and Chromatin
Volume	6
Issue number	1
DOIs	https://doi.org/10.1186/1756-8935-6-36
State	Published - 2013

Bibliographical note

Funding 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).

Keywords

Aging
DNA methylation
Epidermis
Methylome sequencing
Transcriptome sequencing

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10.1186/1756-8935-6-36

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title = "Aging is associated with highly defined epigenetic changes in the human epidermis",

abstract = "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.",

keywords = "Aging, DNA methylation, Epidermis, Methylome sequencing, Transcriptome sequencing",

author = "G{\"u}nter Raddatz and Sabine Hagemann and Dvir Aran and J{\"o}rn S{\"o}hle and Kulkarni, {Pranav P.} and Lars Kaderali and Asaf Hellman and Marc Winnefeld and Frank Lyko",

note = "Funding Information: We thank Andr{\'e} Leischwitz and the DKFZ Genomics and Proteomics Core Facility for sequencing services. We also thank Franz St{\"a}b and Horst Wenck for their support. This work was funded by the BMBF-GerontoSys program through the project AGENET (FKZ0315898).",

year = "2013",

doi = "10.1186/1756-8935-6-36",

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T1 - Aging is associated with highly defined epigenetic changes in the human epidermis

AU - Raddatz, Günter

AU - Hagemann, Sabine

AU - Aran, Dvir

AU - Söhle, Jörn

AU - Kulkarni, Pranav P.

AU - Kaderali, Lars

AU - Hellman, Asaf

AU - Winnefeld, Marc

AU - Lyko, Frank

N1 - Funding 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).

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Aging

KW - DNA methylation

KW - Epidermis

KW - Methylome sequencing

KW - Transcriptome sequencing

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Aging is associated with highly defined epigenetic changes in the human epidermis

Abstract

Bibliographical note

Keywords

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