Breasts typically age more quickly than the rest of
the female body. So suggests a system that may be the most accurate way
yet of identifying a person's age from a blood or tissue sample.
As we age, the pattern of chemical
markings on our DNA changes. Each gene becomes more or less methylated,
that is, they have methyl chemical groups added or removed. This
generally increases or decreases gene expression. The whole process is
known as epigenetics.
Steve Horvath at the University of
California, Los Angeles, and his colleagues have used these changes to
estimate a person's age. To do so, they first performed a detailed
statistical analysis of methylation patterns in 7844 healthy tissue
samples from 51 different types of tissue. The tissue covered a range of
ages – from fetuses to people 101 years old.
Universal ageing
The analysis allowed the team to weed out
methylation patterns that varied between tissues, leaving just those
that are common to all tissues. This enabled them to identify a subset
of 353 specific regions of the genome that became either more or less
methylated with age in almost all types of tissue.
By measuring the total amount of
methylation in these regions, the team was able to create an algorithm
that identified the age of the tissue.
The team validated the algorithm against
thousands more samples of known age. Horvath says the method is twice as
accurate as the next best method of ageing tissue, which is based on the length of telomeres
– tips of chromosomes that "burn down" with age like candle wicks. He
says that his method has a 96 per cent chance of accurately identifying
someone's age to within 3.6 years compared with around 53 per cent for
telomeres.
"What's unique about this study is the
idea that there's a signature of ageing common across tissues in spite
of the significant tissue specificity of DNA methylation patterns,"
comments Moshe Szyf, who studies methylation at McGill University in
Montreal, Canada. "The data point to the possibility that DNA
methylation signatures could be used as robust markers of biological
ageing."
Young at heart
Horvath says that, remarkably, their analysis
shows that some parts of the body age at different rates. When they
used their algorithm on healthy breast tissue from a group of women of
average age 46, for example, it churned out a result that was on average
two to three years older than the woman's actual age. Whereas in two
groups aged 55 and 60 across both sexes, heart tissue appeared nine
years younger than true age.
If it is known where the sample comes
from, it is still possible to accurately predict age after some
straightforward adjustment, says Horvath. However, in general, the
algorithm is most accurate for samples from people under 30 years of
age. "The older one gets, the less accurate it becomes," he says.
Horvath thinks that breast tissue ages
more quickly because of its constant exposure to hormones. Heart tissue
may remain younger, by contrast, because it is constantly regenerated by
stem cells.
Cancerous tissue also appeared to age prematurely, coming out at 36 years older than the person's actual age on average across 20 cancers from 20 different organs.
Because ageing is a risk factor for all
cancers, Horvath suggests that the premature ageing of breast tissue
might explain why it is the most common cancer in women. "It could be so
prevalent because that part of the female body is older," he says.
Blood work
Because the method also works on blood it
might have the potential to be used forensically, to reveal the age of a
murder suspect, suggests Horvath. It might also be used to diagnose
cancer, by revealing accelerated ageing in tissue biopsies.
"The data raises questions about whether
these DNA methylation changes play a causal role in ageing and, if so,
whether epigenetic interventions could reverse these and therefore slow down ageing,"
says Szyf. "The chemical robustness of DNA methylation and the ability
to accurately measure it make it a very attractive tool to study ageing,
which could well be superior to measuring telomere length, which is the
current practice."
Horvath says that further studies comparing telomere and epigenetic ageing could be useful, and hopes the two can be complementary. He also says that the software for his algorithm is openly available so that other researchers can try validating it on their own tissue samples.
Journal reference: Genome Biology, DOI: 10.1186/gb-2013-14-10r115
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