Genetic differences between newborns and centenarians tell cancer tales
The collection of small chemical modifications along a DNA strand – or, the epigenome – can distinguish an infant’s DNA from the DNA of someone around 100 years old.
As we age, the core of our biological being, the sequence of our DNA, remains the same. But more subtle chemical changes to our DNA occur as we age. The scope of these changes can be dramatic, and they may help explain why our risk of cancer and other diseases increases as we get older, ScienceNOW reports.
An international team led by Jun Wang at University of Copenhagen and Manel Esteller at University of Barcelona compared DNA samples taken from a 103-year-old man’s blood and from a newborn boy’s umbilical cord blood.
In each case, they identified millions of locations where the DNA had been modified. These changes took place through a process called methylation:
DNA is made up of four basic building blocks – adenine, thymine, guanine, and cytosine – and the sequence of these nucleotides within a gene determines what protein it makes. Genes can be switched on and off as needed, and the regulation of genes often involves what are called epigenetic mechanisms in which chemical alterations are made to the DNA.
One of the most common of these epigenetic changes involves a methyl group – one carbon atom and three hydrogen atoms – binding to a nucleotide, usually cytosine. In general, this binding, called methylation, turns off the gene in question.
They treated DNA with chemicals and ended up with an epigenetic map showing exactly which DNA sites are methylated and which aren’t (pictured).
- They found a significantly higher amount of cytosine methylation in the newborn than in the centenarian.
- Approximately 80% of all possible locations within the newborn’s DNA were methylated.
- Compared with 73% in the centenarian’s.
- In all, half a million fewer regions were methylated in the centenarian’s DNA than in the infant’s DNA.
- Nearly 18,000 ‘differentially methylated regions’ (DMRs) of the genome were found. More than a third of the DMRs occurred in genes that have already been linked with cancer risk.
They extended the analysis to include DNA from 19 newborns and 19 people in their 90s. They found a similar reduction: older people have a lower amount of cytosine methylation than newborns. Additionally, DNA from middle-aged individuals showed an intermediate level – with 78% methylation.
The degree of methylation decreases in a cumulative fashion over time. Changes in DNA methylation patterns as we age may contribute to diseases where risk increases with age:
In the centenarian, the loss of methyl groups, which turns genes back on, often occurred in genes that increase the risk of infection and diabetes when they are turned on during adulthood. In contrast, the small number of genes in the centenarian that had greater methylation levels were often those that needed to be kept turned on to protect against cancer.
The work was published in the Proceedings of the National Academy of Sciences this week.
Images: PNAS 2012