Dichotomy between the transcriptomic landscape of naturally versus accelerated aged murine hearts

Federica De Majo, Jana-Charlotte Hegenbarth, Frank Ruehle, Christian Baer, Thomas Thum, Martine de Boer, Dirk J. Duncker, Blanche Schroen, Anne-Sophie Armand, Monika Stoll, Leon J. De Windt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We investigated the transcriptomic landscape of the murine myocardium along the course of natural aging and in three distinct mouse models of premature aging with established aging-related cardiac dysfunction. Genome-wide total RNA-seq was performed and the expression patterns of protein-coding genes and non-coding RNAs were compared between hearts from naturally aging mice, mice with cardiac-specific deficiency of a component of the DNA repair machinery, mice with reduced mitochondrial antioxidant capacity and mice with reduced telomere length. Our results demonstrate that no dramatic changes are evident in the transcriptomes of naturally senescent murine hearts until two years of age, in contrast to the transcriptome of accelerated aged mice. Additionally, these mice displayed model-specific alterations of the expression levels of protein-coding and non-coding genes with hardly any overlap with age-related signatures. Our data demonstrate very limited similarities between the transcriptomes of all our murine aging models and question their reliability to study human cardiovascular senescence.

Original languageEnglish
Article number8136
Number of pages14
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 18 May 2020

Keywords

  • NUCLEAR ABNORMALITIES
  • TELOMERE LENGTH
  • DNA-DAMAGE
  • MECHANISMS
  • CANCER
  • EXPRESSION
  • LONGEVITY
  • PREDICTS
  • MUTATION
  • FAILURE

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