Between the body aches and wrinkles, most of us don’t need to be reminded that getting old is the most significant health risk. A new report in Genome Research explains how promoters of certain Polycomb group protein target genes (PCGTs) become increasingly hypermethylated as we age; leaving us more at risk for cancer.
The link between aging and cancer isn’t new and we actually highlighted some related work on aging and DNA methylation recently too (Prolonged Exposure to Life Alters Your DNA Methylation), but researchers from University College London, and USC have delved into what’s behind that correlation. They focused their experiments on DNA methylation in PCGTs, knowing that they are more likely (12-fold) to be methylated in cancer than other genes, and are repressed in stem cells, but then expressed later as cells differentiate.
The group used Illumina’s HumanMethylation27 Infinium microarrays to analyze the DNAm status in over 27,000 CpGs, within promoters of more than 14,000 genes and here is what they found:
- PCGTs are more likely to become methylated with age independent of disease state, sex, tissue or cell type.
- A validated set of 69 PCTG CpG sites that are hypermethylated with age, compiled from 7 data sets and 900 samples.
- The age-PCGT signature can distinguish normal tissue from preinvasive and invasive cancer.
Based on their evidence and other previously published data, the authors hypothesize that PGCTs get progressively methylated as we age, leading to cells with irreversible stem cell features (like unchecked self-renewal) and opening the door for them to turn cancerous. Not exactly a pretty picture, but once researchers learn how to stop the aging process, we should be in the clear. OK, so that one may take a while, but the good news is that smart folks like this team are on it.
Feel young again while you check out all the details in Genome Research, March 2010.