Genomic instability in the naturally and prematurely aged myocardium
Federica De Majo, Leonie Martens, Jana-Charlotte Hegenbarth, Frank Rühle, Magda R. Hamczyk, Rosa M. Nevado, Vicente Andrés, Erika Hilbold, Christian Bär, Thomas Thum, Martine de Boer, Dirk J. Duncker, Blanche Schroen, Anne‐Sophie Armand, Monika Stoll, León J. De Windt
Abstract
Significance Accumulation of DNA variants is considered a cause of organ dysfunction during natural aging. Here, we directly assessed the frequency of DNA damage of the murine myocardium during natural aging and in hearts from four mouse models of premature aging. In contrast to the prevailing dogma, our results provide no evidence for an enrichment in variants in the naturally aging heart until 2 y of age in Hutchinson–Gilford Progeria Syndrome hearts or in hearts with reduced telomere lengths. Accumulation of randomly distributed variants was, however, evident in Ercc1 knockout mice with deficient DNA repair machinery and in the intestine, liver, and lung of naturally aging mice. These results launch avenues to dissect the fundamental biological processes underlying cardiac aging.