Abstract
Retrotransposable elements (RTEs) are interspersed repetitive sequences that represent a large portion of eukaryotic genomes. Ancestral expansions of RTEs directly contributed to the shaping of these genomes and to the evolution of different species, particularly mammals. RTE activity is tightly regulated by different epigenetic mechanisms but this control becomes compromised as cells age and RTEs are reactivated. This dysregulation of RTEs leads to perturbation of cell function and organ and organismal homeostasis, which drives ageing and age-related disease. Environmental stress is associated with both ageing-related characteristics and the epigenetic mechanisms that control RTE activity, with accumulating evidence indicating that RTE reactivation mediates the effects of environmental stressors on ageing onset and progression. A better understanding of how RTEs are reactivated and their subsequent biological roles may help the development of therapies against ageing-related phenotypes and diseases.
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Fig. 1: Impact of RTEs on the evolution of the eukaryotic genome.
Fig. 2: The epigenetic suppression of RTEs.
Fig. 3: The pro-inflammatory activity of RTEs.
Fig. 4: The effects of RTE transcription products on cell function.
Fig. 5: Relationship between RTE silencing and environmental challenges.
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Francesco Della Valle, Pradeep Reddy, Alain Aguirre Vazquez & Juan Carlos Izpisua Belmonte
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Francesco Della Valle
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F.D.V. and P.R. researched data for the article. J.C.I.B., F.D.V., A.A.V. and P.R. contributed substantially to the discussion of the content. All authors wrote the article and reviewed and/or edited the manuscript before submission.
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Della Valle, F., Reddy, P., Aguirre Vazquez, A. et al. Reactivation of retrotransposable elements is associated with environmental stress and ageing. Nat Rev Genet (2025). https://doi.org/10.1038/s41576-025-00829-y
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DOI:https://doi.org/10.1038/s41576-025-00829-y
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