Cancer is the number one cause of death in Korea. However, in the world, cardiovascular disease is overwhelmingly number one.
In Korea, as life expectancy increases and lifestyles become more westernized, the number of patients with cardiovascular disease is increasing quite rapidly.
Cardiovascular diseases are roughly divided into six categories: myocardial infarction, angina pectoris, arteriosclerosis, hypertension, arrhythmia, and congenital heart disease.
Scientists view cardiovascular disease as a kind of aging disease.
It is generally known that high blood pressure and cholesterol levels increase the risk of cardiovascular disease.
However, it is difficult to clearly explain the relationship between aging and cardiovascular disease from this alone.
Why does the risk of cardiovascular disease increase with age?
The direct cause lies in the accumulation of mutations in cardiomyocytes, a study found.
The mutated cardiomyocytes also lost the ability to repair damaged DNA, the researchers found.
The results of this study conducted by scientists at Boston Children’s Hospital were published in the journal Nature Aging on the 11th (local time).
The research team conducted full sequencing of 56 myocardial cell samples using cutting-edge bioinformatics technology and analysis techniques.
The age at death of the patients who donated the cells ranged from infancy to 82 years of age.
However, all deaths from causes related to heart disease were excluded for now.
They compared somatic mutations, or non-inherited mutations, in each cell to see if there were any mutational patterns that might explain the mechanisms of heart disease.
So far, we have never observed single-cell-level somatic mutations in the human heart.
As the age of the donor from whom the cardiomyocytes were collected increased, the number of ‘single-nucleotide variants’ of DNA was also found.
This mutational pattern occurs when there are multiple mutations due to oxidative damage.
Minghui Chen, a cardiologist at Boston Children’s Hospital, said, “A heart that beats without rest requires a lot of energy.”
To make matters worse, these mutations disrupted the repair pathway that normal cells use to repair damaged DNA.
In fact, when the DNA damage of free radicals exceeds the limit, this mechanism does not work properly.
It suggests that with age, the cell’s DNA repair mechanism also breaks down.
The co-corresponding author of the paper, Dr. Christopher Walsh, is considered a pioneer in the fields of ‘single-cell whole genome sequencing’ and bioinformatics, who made a decisive contribution to this research.
Recently, he disclosed a method to determine how much mutation occurred in the brain neurons (neurons) of Alzheimer’s disease patients.
Cells that do not continuously divide, such as heart cells, are usually less prone to mutations.
Cardiomyocytes, however, accumulated mutations at regarding the same or even faster rate than cells that kept dividing.
The rate of mutation accumulation in cardiomyocytes was three times that of brain neurons, an equally non-continuous cell type.
Mutations in cardiomyocytes adversely affected DNA repair pathways as well as genes involved in the cytoskeleton.
Dr. Chen said, “As we get older, the number of mutations in myocardial cells increases, and when it crosses a critical point, heart disease occurs.
This time, the research team looked at only single nucleotide mutations in cardiomyocytes.
This means we don’t know how many other types of mutations there are, such as erroneous insertions or deletions in DNA.
It has also not been able to determine how mutations in cardiomyocytes are directly related to heart disease.
This is because only cardiomyocytes from patients unrelated to heart disease were tested.
The team plans to determine to what extent mutations occur in different types of heart cells during aging.
A study plan is also planned for cancer patients with heart disease.
The research team sees the results of this study as ‘the tip of the iceberg’.
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