An RPMM of pleural tissues (n = 18) resulted in five methylation classes ( Figure 2D ), and class membership was not associated with age; yet, an association between methylation class and asbestos exposure approached significance ( P <0.07).
In fact, recent work has shown an overall trend of increased methylation associated with older age in normal human prostate and colon tissues in several genes [18] , [19] .
In solid tissues (n = 119) we found striking, highly significant CpG island–dependent correlations between age and methylation; loci in CpG islands gained methylation with age, loci not in CpG islands lost methylation with age ( P <0.001), and this pattern was consistent across tissues and in an analysis of blood-derived DNA.