Nature Aging: Aging hearts accumulate mutations and lose ability to repair them

Why does the risk of heart disease increase with age? Known risk factors such as high blood pressure or high cholesterol do not explain all case.

The findings were published Au.

The team, led by Sangita Choudhury, PhD, and August Yue Huang, PhD, of Boston Children's Division of Genetics and Genomics, sequenced the entire genomes of 56 individual cardiomyocytes, who ranged in age from infancy to 82, who died Causes not related to heart diseas.

Classifying mutations in the aging heart

Using sophisticated bioinformatics techniques and analyses, the team compared the number of non-inherited mutations, called somatic mutations, in cells of different ages and looked for mutational patterns, or "signatures," that might shed light on the mechanisms of heart diseas.

"This is the first time that somatic mutations in the human heart have been studied at the single-cell level," Choudhury sai.

The older a cell is, the more changes in a single "letter" (ie, a single nucleotide variation) in its DN.

"Because the heart is beating all the time, it uses up a lot of energy," said Ming Hui Chen, PhD, in the Division of Genetics and Genomics at Boston Children's Hospita.

To make matters worse, the mutation also affected the normal way cells repair DNA damag.

The technically difficult study utilized single-cell whole-genome sequencing and bioinformatics techniques pioneered in the laboratory of D.

In general, cells that do not continue to divide, such as heart cells, are less susceptible to mutation.

"Heart cells also accumulate mutations three times faster than neurons, another cell type that doesn't divid.

In addition to DNA repair pathways, mutations affected genes involved in the cytoskeleton (the scaffolding that gives cells their structure) and other essential cellular function.

"As you age, the more genetic mutations you have, the more detrimental effects that can take the heart over a tipping point and into a diseased state, where it can reach a point where a lot of DNA is damaged and the heart can no longer beat normall.

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The researchers noted that their study only looked for single-nucleotide variants and did not investigate other types of mutations, such as DNA insertions or deletion.

D.

"We also wanted to study different cell types in the heart, and we've only scratched the surface of the iceber.