DNA methylation may be used as a “biological clock” for determining age. Source: http://upload.wikimedia.org/wikipedia/commons/8 /80/DNA_methylation.jpg
Steve Horvath, a biostatistician at UCLA, has analyzed DNA methylation data from several tissue types to come up with a biological measure of age.
Epigenetic controls of gene expression, such as DNA methylation (DNAm), are mechanisms that are not explicitly coded in a nucleotide sequence. Methylation occurs when the addition of methyl groups to DNA’s nitrogenous base (usually cytosine) block polymerase enzymes from transcribing the DNA. Additionally, it is well known that various genes become either “hypermethylated or hypomethylated with age,” thus indicating that methylation and aging are inextricably linked (1).
However, while methylation levels change with age, there was no known useful relationship between DNAm levels and age. Horvath analyzed methylation data from 8,000 samples of 51 different tissue types in order to zero in on the biomarkers that have age-dependent DNAm levels. His mathematical analysis led him to discover 353 such biomarkers (2).
The 353 biomarkers are sequences of nucleotides called CpGs that have a cytosine next to a guanine on a single strand of DNA. Horvath then performed a weighted-average calculation on the methylation levels of these 353 biomarkers to produce an “epigenetic clock” (1). In order to test the accuracy of his clock, he analyzed the difference between DNAm age and actual chronological age across various tissue and cell types.
Horvath first looked at methylation levels among various blood cell types and concluded “DNAm age does not vary significantly across sorted blood cells from healthy male subjects”(1). Furthermore, Horvath noted that the “age predictor works well in individual cell types. (1)” That means that DNAm levels change in specific cell types over time. This idea is further supported by the fact that there is a high correlation between DNAm age and chronological age in other cells such as neurons.
However, there are several tissue types that have a low correlation between DNAm and chronological age. For example, heart tissue tends to have a lower DNAm age compared to chronological age; Horvath speculates that it is because stem cells are steadily employed to form new cardiac tissue. Furthermore, DNAm levels in cancerous tissue generally have a weak correlation with chronological age because the difference between DNAm age and chronological age is greater than normal. Thus, tissues and organs that undergo consistent cell division or regeneration will probably have a DNAm age that is not highly correlated with chronological age.
Currently, doctors have no objective way to measure how “old” a patient’s body is, but Horvath’s clock could change all that (2). Before the scientific community can figure out ways to slow aging, it first must be able to measure it. Horvath’s clock seems to be the first step in that direction.
References
1. S. Horvath, DNA Methylation Age of Human Tissues and Cell Types (October 21, 2013). Available at http://genomebiology.com/2013/14/10/R115 (October 25, 2013).
2. An Update on Using DNA Methylation to Measure Age (October 22, 2013). Available at https://www.fightaging.org/archives/2013/10/an-update-on-using-dna-methylation-to-measure-age.php (October 25, 2013).
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