The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 16 No. 7 • August 2013


Genome-Wide Methylation Profiles of 656 Individuals
Reveals Epigenetic Changes in Aging

Changes in Methylation Predict Age
and Are Associated with Complex Diseases

At a completely different level than the human genome, the human methylome represents a map of the methylation of DNA, which determines how genes are expressed. Consequently, it helps reveal how alterations in the regulation of DNA transcription (whether a gene is turned on or off) takes place throughout life. For example, a new paper1 discusses the fact that “epigenetic drift” takes place in identical twins, where the methylation marks increasingly differ with age, causing them to “drift” from their starting point with identical DNA at birth. The DNA remains the same (except for mutations) but is expressed differently as a result of methylation-induced changes.

As the authors1 put it (and we couldn’t have put it better): “the idea of the epigenome as a fixed imprint is giving way to the model of the epigenome as a dynamic landscape that reflects a variety of chronological changes.”

In this fascinating paper, the researchers have determined DNA methylation at more than 450,000 CpG markers (where the methylation takes place) from the whole blood of 656 human individuals, aged 19 to 101. Their model, based upon the data they got from these measurements, can be used to determine the rate at which an individual’s methylome ages.1 They found an optimal model consisting of a selected set of 71 methylation markers; this model was highly predictive of age, with a correlation between age and predicted age of 96% with an error of 3.9 years.1 “Nearly all markers in the model lay within or near genes with known functions in aging-related conditions, including Alzheimer’s disease, cancer, tissue degradation, DNA damage, and oxidative stress.”

Another finding was that the methylome of men appeared to age approximately 4% faster than that of women. The scientists also compared the methylome derived from whole blood to that of breast, kidney, lung, and skin samples and found strong predictive power for chronological age for these tissues as well, although noting some linear offset from the expected age prediction. Another finding was that “tumors appear to have aged 40% more than matched normal tissue from the same individual. Accelerated tumor aging was apparent regardless of the primary tissue type.” Moreover, the researchers compared the methylation changes of tumors to normal tissue, examining all 70,387 age-associated markers, where 44% tend to increase and 56% tend to decrease with age. The tumor markers coincided with older values by 74% of the markers regardless of the trending direction (e.g., whether they increased or decreased).

The scientists even determined (using a mathematical model developed by Shannon and Weaver2), the increase in entropy (loss of information content) in the methylome over time. As the researchers explain it, “[a]n increase in entropy of a CpG marker means that its methylation state becomes less predictable across the population of cells (i.e. its methylation fraction tends toward 50%).” The researchers found a highly significant increase in methylome entropy over the sample cohort. “Furthermore, extreme methylome entropy for an individual was highly correlated with accelerated aging rate …”1

The scientists suggest that this model could be used to assess the aging rate of an individual and to determine whether diet or environmental factors can accelerate or or retard the aging process and diseases of aging.

This is a remarkable new development that is just now beginning to be used in aging research. Better yet would be if such measurements were to become inexpensive enough for individuals such as ourselves to monitor our own aging.

Reference

  1. Hannum et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 49:359-67 (2013).

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