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AGECAN - Interespecies conservation of brain specific DNA methylation in aging and cancer

ABSTRACT: Aging is one of the main risk factors associated with the development of cancer. These two processes have been extensively investigated from the epigenetic perspective and consequently analogous epigenetic alterations have been identified for both, providing explanations on the possible molecular links between them. However, there is a need to study aging- and cancer-associated epigenetic patterns in a systematic manner to facilitate an integrated comparison between the two processes. In addition, it is essential to also confirm whether aging- and cancer-associated epigenetic alterations are equivalent in human and mouse models, as the latter are the main experimental proxy of human biology.In this study we sought to perform a systematic, integrated and intercomparable analysis of the DNA methylation dynamics associated to cancer and aging in both human and mouse. To this end, we profiled the brain methylomes of young and old, normal and tumoral brain samples from human and mouse by reduced-representation bisulfite sequencing (RRBS), which provided a robust and interspecies-comparable platform for these type of analyses. This data set only contains files involving human specimens. Accompanying mouse data can be downloaded from the ENA database under the accession number PRJEB41460.

PROVIDER: EGAS00001004851 | EGA |

REPOSITORIES: EGA

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Project description:Background: Skin aging is associated with intrinsic processes that compromise structure of the extracellular matrix while promoting loss of functional and regenerative capacity. These processes are accompanied by a large-scale shift in gene expression, but underlying mechanisms are not understood and conservation of these mechanisms between humans and mice is uncertain. Results: We used genome-wide expression profiling to investigate the aging skin transcriptome. In humans, age-related shifts in gene expression were sex-specific. In females, aging increased expression of transcripts associated with T-cells, B-cells and dendritic cells, and decreased expression of genes in regions with elevated Zeb1, AP-2 and YY1 motif density. In males, however, these effects were contrasting or absent. When age-associated gene expression patterns in human skin were compared to those in tail skin from CB6F1 mice, overall human-mouse correspondence was weak. Moreover, inflammatory gene expression patterns were not induced with aging of mouse tail skin, and well-known aging biomarkers were in fact decreased (e.g., Clec7a, Lyz1 and Lyz2). These unexpected patterns and weak human-mouse correspondence may be due to decreased abundance of antigen presenting cells in mouse tail skin with age. Conclusions: Aging is generally associated with a pro-inflammatory state, but we have identified an exception to this pattern with aging of CB6F1 mouse tail skin. Aging therefore does not uniformly heighten inflammatory status across all mouse tissues. Furthermore, we identified both intercellular and intracellular mechanisms of transcriptome aging, including those that are sex- and species-specific. We used Affymetrix microarrays to evaluate genome-wide expression in tail skin from young (5 month) and old (30 month) CB6F1 mice (males and females). Genome-wide expression was evaluated in tail skin from young (5 months) and old (30 months) CB6F1 mice of both sexes. Samples were collected simultaneously but RNA samples were processed in two separate batches.

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AGECAN - Interespecies conservation of brain specific DNA methylation in aging and cancer

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