Somatic mutations in single human cardiomyocytes reveal age-associated DNA damage and widespread oxidative genotoxicity
The accumulation of somatic DNA mutations over time is a hallmark of aging in many dividing and nondividing cells but has not been studied in postmitotic human cardiomyocytes. Using single-cell whole-genome sequencing, we identified and characterized the landscape of somatic single-nucleotide variants (sSNVs) in 56 single cardiomyocytes from 12 individuals (aged from 0.4 to 82 years). Cardiomyocyte sSNVs accumulate with age at rates that are faster than in many dividing cell types and nondividing neurons. Cardiomyocyte sSNVs show distinctive mutational signatures that implicate failed nucleotide excision repair and base excision repair of oxidative DNA damage, and defective mismatch repair. Since age-accumulated sSNVs create many damaging mutations that disrupt gene functions, polyploidization in cardiomyocytes may provide a mechanism of genetic compensation to minimize the complete knockout of essential genes during aging. Age-related accumulation of cardiac mutations provides a paradigm to understand the influence of aging on cardiac dysfunction.
| Errataetall: |
CommentIn: Nat Aging. 2022 Aug;2(8):686-687. - PMID 36471785 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2 |
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| Enthalten in: |
Nature aging - 2(2022), 8 vom: 18. Aug., Seite 714-725 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Choudhury, Sangita [VerfasserIn] |
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| Links: |
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Journal Article |
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| Anmerkungen: |
Date Completed 18.07.2023 Date Revised 18.07.2023 published: Print-Electronic CommentIn: Nat Aging. 2022 Aug;2(8):686-687. - PMID 36471785 Citation Status MEDLINE |
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| doi: |
10.1038/s43587-022-00261-5 |
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NLM345687256 |
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| 245 | 1 | 0 | |a Somatic mutations in single human cardiomyocytes reveal age-associated DNA damage and widespread oxidative genotoxicity |
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| 500 | |a CommentIn: Nat Aging. 2022 Aug;2(8):686-687. - PMID 36471785 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The accumulation of somatic DNA mutations over time is a hallmark of aging in many dividing and nondividing cells but has not been studied in postmitotic human cardiomyocytes. Using single-cell whole-genome sequencing, we identified and characterized the landscape of somatic single-nucleotide variants (sSNVs) in 56 single cardiomyocytes from 12 individuals (aged from 0.4 to 82 years). Cardiomyocyte sSNVs accumulate with age at rates that are faster than in many dividing cell types and nondividing neurons. Cardiomyocyte sSNVs show distinctive mutational signatures that implicate failed nucleotide excision repair and base excision repair of oxidative DNA damage, and defective mismatch repair. Since age-accumulated sSNVs create many damaging mutations that disrupt gene functions, polyploidization in cardiomyocytes may provide a mechanism of genetic compensation to minimize the complete knockout of essential genes during aging. Age-related accumulation of cardiac mutations provides a paradigm to understand the influence of aging on cardiac dysfunction | ||
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Huang, August Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Junho |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zinan |e verfasserin |4 aut | |
| 700 | 1 | |a Morillo, Katherine |e verfasserin |4 aut | |
| 700 | 1 | |a Maury, Eduardo A |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Jessica W |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Michael B |e verfasserin |4 aut | |
| 700 | 1 | |a Lodato, Michael A |e verfasserin |4 aut | |
| 700 | 1 | |a Araten, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Hilal, Nazia |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Eunjung Alice |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ming Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Walsh, Christopher A |e verfasserin |4 aut | |
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