Increased hippocampal epigenetic age in the Ts65Dn mouse model of Down Syndrome.

We found a CpG probe (cg04235075) mapping within the HSF4 gene that showed a trend toward hypermethylation in people with DS ( GSE63347 , nominal p -value = 0.05, not significant after FDR correction) ( Supplementary Figure S1 ).

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Ts65Dn mice showed a higher DNAge variance compared to euploid mice, although they did not reach statistical significance ( F -test p -value = 0.1231).

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An in-depth analysis of the sites making up the DNAge® epigenetic clock showed that some sites and regions showed a nominally significant association with trisomy.

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Similarly, the CpGs that were differentially methylated between trisomic and euploid mice were significant or marginally significant when restricting the statistical analysis to male animals.

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