Della Valle Francesco, Reddy Pradeep, Aguirre Vazquez Alain, Izpisua Belmonte Juan Carlos
Altos Labs, San Diego Institute of Science, San Diego, CA, USA.
Nat Rev Genet. 2025 Apr 2. doi: 10.1038/s41576-025-00829-y.
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.
逆转座元件（RTEs）是散布的重复序列，占真核生物基因组的很大一部分。RTEs的祖先扩张直接促成了这些基因组的形成以及不同物种（尤其是哺乳动物）的进化。RTE活性受到不同表观遗传机制的严格调控，但随着细胞衰老和RTEs重新激活，这种控制会受到损害。RTEs的这种失调会导致细胞功能、器官和机体稳态的紊乱，从而推动衰老和与年龄相关的疾病。环境应激与衰老相关特征以及控制RTE活性的表观遗传机制都有关联，越来越多的证据表明，RTE重新激活介导了环境应激源对衰老起始和进展的影响。更好地了解RTEs如何被重新激活及其后续的生物学作用，可能有助于开发针对与衰老相关表型和疾病的疗法。
