A new Review article published in Genome Biology and Evolution (Merenciano et al. 2025) focuses on the relationship between transposable elements and aging. Senior author Cristina Vieira (Université Claude Bernard Lyon 1, France) answers some of our questions to shed light on the new study.

1. What do you think makes transposable elements such a compelling force in the ageing process?

What makes transposable elements a compelling force in the ageing process is their ability to reshape the genome. Transposable elements are DNA fragments with the ability to move within the genome present in all eukaryotic genomes. They can produce a wide range of functional effects - ranging from passive genomic persistence to active mutagenesis. Thanks to their mobile and repetitive nature transposable elements contribute significantly to both genetic and epigenetic variation. Their activity can compromise genome stability, modulate gene expression, disrupt regulatory networks, and produce epigenetic modifications, all of which are hallmarks of ageing. Moreover, an increase in TE activity has been found with age in some organisms, potentially intensifying molecular damage and cellular dysfunction. Therefore, TEs could represent an important factor in the biology of ageing that needs to be studied deeper.

2. In your experience, what are the most promising experimental or conceptual approaches for disentangling the effects of TE activity from other ageing-related genomic changes?

One of the strategies that would help disentangling the effects of transposable element activity from other ageing-related genomic changes is the application of single-cell and tissue-specific analyses. Since transposable element activation can vary between different cell types and tissues, single-cell transcriptomic and epigenomic profiling are good techniques to identify where and when specific transposable elements become active, and how these events correlate with changes in chromatin state or gene expression. This spatial and temporal resolution would shed light on distinguishing transposable element-driven effects from more generalized, systemic genomic alterations associated with ageing.

Functional manipulation of transposable elements through CRISPR-based approaches, for example, can offer a direct way to assess their causal role in ageing phenotypes as well. By activating or repressing specific transposable elements it would be possible to determine their impact on genome stability, inflammation, or cellular senescence.

3. What do you think is still most misunderstood about the role of TEs in shaping long-term organismal health?

To better understand the role of transposable elements in long-term health, further research is needed to investigate the function of non-coding RNAs derived from them. Transposable elements can produce small non-coding RNAs (such as piRNAs) that regulate gene expression. Yet, the role of these small RNAs in ageing processes is still poorly understood. Furthemore, the potential for transposable elements to trigger inflammatory responses is another aspect that would need more investigation. There is evidence showing that, when expressed, transposable elements can activate innate immune pathways leading to inflammation, which is a hallmark of ageing. Nevertheless, evidence linking transposable element activity to this process remains anecdotal. Also, it seems obvious that sex of the individuals should be taken into account when performing individual therapies or analysis, as TE could be mobilised in a sex specific manner.

4. Is there anything else you would like to say about your research for the Highlight article?

Future research should aim to clarify the role of TE activation in aging across different species and sexes, especially given the well-documented sex differences in lifespan. Additionally, investigating how TEs interact with epigenetic regulators during aging holds great potential for the development of novel therapeutic interventions, where targeted modulation of TE activity could help alleviate age-related dysfunctions. Also, the variation of the TE content and position in genomes is a strong challenge for the analysis but also gives the genome a huge plasticity that needs to be taken into account.

Want to learn more about transposable elements and aging? Check the new article by Merenciano et al. in Genome Biology and Evolution:

Merenciano M, Larue A, Garambois C, Nunes WV, Vieira C. Exploring the relationship of transposable elements and ageing: causes and consequences. Genome Biol Evol. 2025:17(6):evaf088. https://doi.org/10.1093/gbe/evaf088