A new way to measure cellular age has been developed by scientists at Van Ardel Research Institute (VARI) and Cedars Sinai. According to the team this new method may lead to better, simpler screening and monitoring methods for cancer and other diseases.
The findings, published today in Nature Genetics, reveal progressive changes that continue throughout a person's life, correlating with cellular rather than chronological age and foreshadowing alterations found in cancer cells.
The work builds on a 2011 discovery by Benjamin Berman of Cedars-Sinai and Peter Laird of VARI that first determined loss of methyl groups occurs in specific areas of the genome in cancer. However, the techniques used at that time could not detect this process occurring in normal cells.
"Our cellular clock starts ticking the moment our cells begin dividing," Laird said. "This method allows us to track the history of these past divisions and measure age-related changes to the genetic code that may contribute to both normal aging and dysfunction."
Despite undergoing elaborate biological quality control checks, each cell division chips away at the genome's integrity, leaving behind an accumulating number of changes. Chief among these is a dramatic shift in the number and location of methyl groups on the genome, part of a process that begins during fetal development and continues throughout a lifetime.
"What is striking about the results from our new method is that they push back the start of this process to the earliest stages of in utero development," Berman said. "That was completely surprising, given the current assumption that the process begins relatively late on the path to cancer. This finding also suggests that it may play a functional role relatively early in the formation of tumors."
While loss of DNA methyl groups, known as hypomethylation, is a common feature of many cancers, it is more profound in cancers that arise in tissues with a high turnover rate, such as the skin and the epithelium. It also features prominently in pediatric cancers such as medulloblastoma.
"Tissues with higher turnover rates are typically more susceptible to cancer development simply because there are more opportunities for errors to accumulate and force the change from a normal cell to a malignant one," Hui Shen of VARI said. "What we're seeing is a normal process—cellular aging—augmented and accelerated once a cell becomes cancerous. The cumulative effect is akin to a runaway freight train."