Shenzhen, China (Scicasts) – An international study, conducted by Bellvitge Biomedical Research Institute (IDIBELL), BGI, and other collaborators, demonstrates that the DNA methylomes between newborns and centenarians are different, shedding important new light on how epigenetic marks degrade during ageing.
The latest study was published online in the National Academy of Sciences (PNAS) on June 11, 2012.
The biology, physiology and medicine related with longevity and ageing have been the research focus for decades. Scientists have discovered that genetic factors only contribute about 10 percent to longevity, while environmental factors contribute about 90 percent. Moreover, many identical twins studies have shown that environmentally induced differences are usually acquired via the epigenome.
Knowing that epigenetic modifications, especially DNA methylomes, are involved in numerous biological processes such as in human ageing and diseases, researchers in this study performed whole-genome bisulfite sequencing (WGBS) and compared the epigenetic information underlying the newborns, middle-aged persons and centenarians.
Through the analysis, they found that approximately 80% of all possible locations within the newborn's DNA were methylated, but only 73% of the locations in the centenarian's DNA were methylated. In all, methylated regions in the centenarian's DNA were half a million fewer than that in the infant's DNA. The regions include promoters, exon, intron, and intergenic elements, suggesting a regulated gene expression pattern in the centenarian.
The researchers extended their analysis to include DNA from larger groups of newborns and nonagenarians, and found a similar reduction in methylation of the nonagenarian DNA. Furthermore, analysis on DNA from middle-aged individuals revealed an intermediate level of methylation that fell between the two age extremes. All the results support a model of human ageing along with small changes in the epigenome, such as the varying DNA methylation, can accumulate over time and lead to broader changes in gene expression and cell function.
Dr. Ning Li, Director of BGI Europe, said, “The accumulative regulation of DNA methylomes may serve as one of the key marks to track human’s ageing process. Our study further identified that epigenetic modifications played a crucial role in the ageing mechanism. We look forward to achieving more breakthroughs in epigenomics research.”
Dr. Manel Esteller, PI of this project and Director of Cancer Epigenetics and Biology Program (PEBC), IDIBELL, said, “The research represents one of the few DNA methylation studies developed at a single-base resolution and the first one that analyzes the complete DNA methylome of newborns and centenarians. It provides important clues for the understanding of longevity, ageing and their associated diseases, such as cancer.”