Identical twins lose some fundamental similarities as they grow older

Jul 11 2005

Identical twins lose some fundamental similarities as they grow older, a new study reports. They may start to look and act less alike. The changes could leave one twin susceptible to diseases like cancer, while the other twin remains healthy.

Researchers report in this week's Proceedings of the National Academy of Sciences that these differences may stem from changes in the epigenome. The epigenome refers to chemical modifications in genes that don't directly affect a gene's DNA but result in changes in gene expression.

Scientists think that chemical exposure, dietary habits and environmental factors may all have epigenetic affects.

Most epigenetic changes are normal and may explain why pairs of twins lose some of their identical attributes as they age. But learning how these modifications affect cells may also shed light on how cancer progresses and develops, said Christoph Plass, a study co-author and an associate professor of molecular virology, immunology and medical genetics at Ohio State University.

Plass and Yue-Zhong Wu, a research associate also at Ohio State , helped a team of European scientists analyze epigenetic changes in twins' genomes. The group was led by Manel Esteller, a researcher with the Spanish National Cancer Center in Madrid.

The researchers studied 40 pairs of twins recruited in Spain , Denmark and the United Kingdom ; 25 of the pairs were female. The youngest set of twins was 3, and the oldest pair was 74. All of the participants were asked to complete questionnaires about their health, eating habits, physical activity, history of prescription medication use and tobacco, alcohol and drug consumption.

The researchers also drew blood samples from each participant in order to analyze and compare similarities and differences in the epigenome.

Results from the blood tests – and from the questionnaires – showed that the youngest set of twins had the most identical genomes. But that wasn't true for the oldest pairs of twins. Genetically speaking, these twins were the least alike.

The process that alters gene expression and behavior without changing a gene's DNA sequence is called methylation. Plass, who is also part of the human cancer genetics program at Ohio State, studies methylation in both normal and cancer cells in hopes of better understanding how the process affects the beginning and progression of the disease.

"Methylation is important for normal cellular development," Plass said. "It can help protect the integrity of a DNA sequence. But certain changes in the regulation of DNA methylation could have fatal consequences for a cell or individual."

Identical twins are born with an identical set of genes. Studying genetic differences in twins may give Plass and his colleagues insight into how methylation is regulated.

"One would expect identical twins to develop and express genes at the same levels, but in fact this changes over time," Plass said. "We think that methylation plays a genome-wide role in these changes."

Scientists think that foods, exposure to chemicals, physical activity levels and aging may all contribute to methylation in cells. But they don't understand how changes in DNA methylation occur, or how the process is regulated.

The DNA analysis in this study showed that twins who had spent less of their lives together, or had greater differences in their health and medical histories, had the greatest amount of methylation.

The next step for Plass is to compare the findings of this study to what he sees in cancer cell cultures in his laboratory.

"Nearly every tumor, every human malignancy shows changes in DNA methylation that mess up gene expression," he said. "If we understand what regulates methylation patterns, then we may be able to develop better treatment options for cancer."

The researchers received financial support for this work from the Foundation of the Spanish Association Against Cancer.

Plass, Yu and Esteller conducted the study with researchers from Spain, Sweden, Denmark and the United Kingdom.