Somatic mutations in single human cardiomyocytes reveal age-associated DNA damage and widespread oxidative genotoxicity.
Level 5 - mechanism / opinion, no new human data
Level 5 by design analogy for basic bench research and ex vivo single-cell genomic profiling of human tissue.
PubMed 36051457 · doi:10.1038/s43587-022-00261-5
What was done
Single-cell whole-genome sequencing was conducted to profile somatic single-nucleotide variants (sSNVs) in 56 single cardiomyocytes collected from 12 human donors aged 0.4 to 82 years.
What was found
Cardiomyocyte sSNVs accumulated with age at rates faster than those observed in many dividing cell types and nondividing neurons. Distinctive mutational signatures implicated defective mismatch repair as well as failed base excision repair and nucleotide excision repair of oxidative DNA damage. No exact quantitative rates or numerical values were provided in the abstract.
Why it matters
This study establishes that human postmitotic heart muscle cells accumulate somatic DNA mutations throughout aging, primarily driven by oxidative genotoxicity, suggesting a mechanistic link between somatic mutation burden and age-related cardiac dysfunction.
Limits
The sample size is very small (12 individuals and 56 total single cells). The cross-sectional, post-mortem design precludes longitudinal tracking within individuals, and the abstract reports no direct functional assessments of cardiac tissue or clinical cardiac outcomes.
Cited by
- supports As humans age, all cells throughout the body accumulate somatic mutations.