Friday, May 27, 2016

Epigenetic modifications of aging have weak direct link on the expression profile

 Steve Horvath reported he had found no universal transcription profile signature of aging.
However there is clearly and aging phenotype of cells. I mean functional decline of the cell. (think of immunosenescene for starters)
Maybe this is caused by transcriptional noise resulting from hypomethylation of repetitive elements (and others)?

Study
Longitudinal epigenetic and gene expression profiles analyzed by three-component analysis reveal down-regulation of genes involved in protein translation in human aging

Fibroblast samples from same person after 10+ years analysed for expression, DNA methylation and certain histone modifications. Shockingly very weak correlation between upregulated sequences and methylation or histone modification.
Expression profile changes match phenotype changes of aging (metalloproteins upregulated , collagen downregulated).

Previous entry concluded stem cells differ not in DNA methylation but in transcription profiles
Maybe its the plasticity and potency of stem cells that is affected by the epigenetic clock by methylating PRC targets. What we see in expression profiles of fibroblasts is the profile of fully differentiated cells, probably different from stem cell profiles.

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