Age-related changes in epigenetic profile of white blood cells in Indian population

Epigenome is a dynamic landscape that displays a variety of biochemical changes induced by environmental exposure over time. Epigenomic profile thus is a better measure of age of an organism as it reflects physiological age rather than chronological age of the individual. Molecular markers that provide an insight into the epigenetic changes accompanying aging, can help in prediction and monitoring of the process. In this context, profiling of histone methylation status during aging, presents us with the opportunity to understand the physiologically accumulated epigenetic changes. In the present study, we have carried out the profiling of lysine methylation of histone H3, at the positions 4 and 27 (H3K4me3 and H3K27me3) in young (~20 years) and old (~60 years) human white blood cell samples. We report novel characteristics of the epigenetic loci that are lost or gained with age. Interestingly, we find a few sites in the genome that switch their epigenetic status with age, as they are marked with contrary histone methylation marks in old individuals as compared to young. Specifically, loss of the transcriptionally repressive mark of H3K27me3 and gain of permissive H3K4me3 marks at the same position in the genome is observed. Interestingly, several of these switching loci occur around genes involved in chemical carcinogenesis, indicating carcinogenic chemicals as one of the common environmental factor causing changes in the epigenetic landscape with age. We thus report a class of age-related epigenetic elements that appear not to be acquired by simple epigenetic drift but by environmental stress management over decades and possibly play an important role in manifestation of aging phenotype.