biostudies-literatureDe Majo FEuropean Research CouncilDeutsche ForschungsgemeinschaftZonMwAFM-TéléthonHartstichtingEC | Horizon 2020e2022974118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8433522biostudies-literatureUnknown118(36)Genomic instability, the unresolved accumulation of DNA variants, is hypothesized as one of the contributors to the natural aging process. We assessed the frequency of unresolved DNA damage reaching the transcriptome of the murine myocardium during the course of natural aging and in hearts from four distinct mouse models of premature aging with established aging-related cardiac dysfunctions. RNA sequencing and variant calling based on total RNA sequencing was compared between hearts from naturally aging mice, mice with cardiomyocyte-specific deficiency of <i>Ercc1</i>, a component of the DNA repair machinery, mice with reduced mitochondrial antioxidant capacity, <i>Tert</i>-deficient mice with reduced telomere length, and a mouse model of human Hutchinson-Gilford progeria syndrome (HGPS). Proceedings of the National Academy of Sciences of the United States of AmericaGenomic instability in the naturally and prematurely aged myocardium.PMC8433522TH903/22-1JCT2016 EXPERT2014T105918-156-47917.14.363311549LONGHEART813716CVON18802Hamczyk MRSchroen BMartens Lde Boer MNevado RMDe Majo FThum TAndres VHilbold ERuhle FDe Windt LJArmand ASBar CDuncker DJHegenbarth JCStoll MfalseGenomic instability in the naturally and prematurely aged myocardium.Genomic instability, the unresolved accumulation of DNA variants, is hypothesized as one of the contributors to the natural aging process. We assessed the frequency of unresolved DNA damage reaching the transcriptome of the murine myocardium during the course of natural aging and in hearts from four distinct mouse models of premature aging with established aging-related cardiac dysfunctions. RNA sequencing and variant calling based on total RNA sequencing was compared between hearts from naturally aging mice, mice with cardiomyocyte-specific deficiency of <i>Ercc1</i>, a component of the DNA repair machinery, mice with reduced mitochondrial antioxidant capacity, <i>Tert</i>-deficient mice with reduced telomere length, and a mouse model of human Hutchinson-Gilford progeria syndrome (HGPS). 2021-01-01T00:00:00Z2021 Sep2026-07-16T16:06:47.364Z2025-04-05T14:04:27.295ZS-EPMC84335223446561710.1073/pnas.2022974118