External factors like the Sun and smoking can harm your DNA by causing mutations, a process that occurs in spurts and bursts. But this process isn't limited to environmental triggers: As cells grow and divide, internal factors also cause the cell to continuously generate mutations at a constant rate. These steady mutations, which occur in a “clock-like” way, correlate to a person’s age: The older you are, the more mutations you acquire.
Researchers have discovered not one, but two of these clock-like mutational processes, and determined the rate at which they tick. This steady ticking could be responsible for many different types of cancer, and might even have a role in aging. It also lends to the possibility that if the clock could be slowed, then so could the risk of developing cancer. Perhaps, tantalizingly, so could the aging process.
“This is a hugely exciting finding as it solves a longstanding question,” says Dr. Ludmil Alexandrov, who co-authored the paper published in Nature Genetics. “Not only has this study proved that mutational molecular clocks exist, it has also shown that there are two separate clock processes that are constantly degrading DNA. How fast these clocks tick in a cell may well determine both the ageing of this cell and the likelihood for it to become cancerous.”
The researchers started by looking at the DNA sequences of over 10,000 individual cancer samples, which represented 36 types of the disease. From this, they discovered just over 30 different mutational “signatures,” or stretches of DNA displaying distinct patterns of mutation, which led to the cancers forming. Furthermore, two of these had “clock-like” features. They showed a correlation between the number of mutations within the sample, and the age of the person from which it was taken, and have been named “signature 1” and “signature 5.”
Because of this steady rate at which the mutations have been accumulating, the researchers were able to effectively look back to when the cell was healthy and calculate the speed at which the “clocks” ticked. While they found that signatures 1 and 5 acquired mutations at a constant rate, this rate was not only different between the two signatures, but also between cell types. So for example, the rate of mutation, or the speed at which the clock ticked, was highest for signature 1 in stomach and colorectal cells, but lowest in breast cells.
The researchers are yet to determine if these mutational clocks tick at the same rate for all of us, or if we’re all running to our own time. But in theory at least, if doctors could calculate the rate at which these mutations are ticking, they could predict the time that they might become cancerous. Not only that, but it also raises the possibility that the clock could be slowed.
