BOSTON — Love songs often suggest protecting your heart, and that advice couldn’t be any more truer when it comes to getting old. We’re not talking about a broken heart of course, but rather, a weakened one. A new study from Boston Children’s Hospital reports that an aging heart has an increased risk of genetic mutations that can lead to heart disease.
What’s more, researchers say older hearts tend to lose the ability to repair and get rid of damaging mutations.
Study authors used bioinformatic techniques and analyses to compare the number of non-inherited mutations called somatic mutations in 56 heart muscle cells, known as cardiomyocytes. The cardiomyocytes came from 12 people ranging from infancy to 82 years old that died from noncardiovascular events. The focus was to look for evidence of mutations in cells of different ages that could point to heart disease.
“This is the first time somatic mutations have been looked at in the human heart at the single-cell level,” says co-first author Dr. Sangita Choudhury, a researcher in the Division of Genetics and Genomics at Boston Children’s, in a statement..
Researchers say that older cells tended to have more single “letter” changes, called single-nucleotide variants, that switches up a cell’s genetic code. Upon closer examination, the team traced the mutations to the effects of oxidative damage.
“Because the heart is always pumping, it uses a lot of energy,” explains co-senior author Dr. Ming Hui Chen, a cardiologist in the Division of Genetics and Genomics and Department of Cardiology. “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 mutations also injured pathways cells use to repair DNA damage. Because cellular repair processes tend to be less effective as people age, oxidative damage may have accelerated this timeline.
Heart cells are more susceptible to mutations they are some of the few types that do not continue to divide. Compared to dividing cell types, cardiomyocytes accumulated mutations at a faster rate of 100 new mutations per year per cell. Heart cells also gather more mutations than other non-dividing cells like neurons.
Mutations caused by oxidative damage altered other cell parts including cell structure and other basic cell functions. “As you age and get more mutations, you’re adding deleterious effects that might push the heart past a tipping point into disease,” says Dr. Chen. “It may get to a point where so much DNA is damaged that the heart can no longer beat well.”
While this study only focused on type of mutation, the team has plans to look at the prevalence of DNA insertion or deletions. They also want to see how other diseases, such as cancer or other heart conditions, impact at the mutation rate in heart muscle cells. “We also want to look at different cell types in the heart,” says Dr. Choudhury. “We’ve only touched the tip of the iceberg.”
The study is published in the journal Nature Aging.