Key Points:
- Scientists from Boston Children’s Hospital sequenced the genome of heart cells of young and old to compare mutations.
- Scientists noticed more genetic mutations in the cells of aged hearts, possibly due to oxidative stress.
- The mutations also inhibited the cells’ ability to repair damaged DNA.
Researchers from Boston Children’s Hospital spearheaded a novel study that helps explain the link between an increased risk of heart disease and old age. The study, published in Nature Aging, attributes the correlation to genetic mutations that concentrate on heart muscle as we age. The basis of the study involved sequencing the genomes of cardiomyocytes, heart muscle cells that oversee contractions in the heart.
The researchers used advanced computer technology to study somatic mutations in the cardiomyocytes of hearts from donors aged between infancy and 82 years. Somatic mutations are not hereditary, instead formed only after conception. The study marks the first time that researchers looked for mutational “signatures” in the heart’s single cells.
Comparing the somatic mutational “signatures” revealed that the older heart cells contained a larger number of single-nucleotide variants, which arise when the DNA sequence is modified by one nucleotide. Researchers believe that exposure to free radicals may contribute to the presence of those variants.
“Because the heart is always pumping, it uses a lot of energy,” says Ming Hui Chen, MD, MMSc, a cardiologist at Boston Children’s. “This energy production creates chemical byproducts known as reactive oxygen species or ROS. When levels of ROS get too high, they can damage DNA.”
The human heart is composed of cells that become senescent as they mature -meaning they stop dividing. Usually, senescent cells are less prone to developing mutations. The research team discovered, however, that cardiomyocytes developed mutations at rates the same as or higher than those of dividing cells.
The researchers found that the somatic mutations had a negative effect on the cardiomyocytes’ ability to repair damaged DNA. Additionally, they discovered that the cells’ cytoskeleton, which is responsible for shaping the cells, was compromised by the presence of these mutations.
In future studies, the researchers plan to include other types of mutations, in addition to examining heart cells from patients who suffered from various cardiovascular diseases.