SCIENTIFIC RESEARCH

Epigenetic resilience in axolotls unlocks longevity insights

15.01.2025

Axolotls exhibit stable DNA methylation beyond early life, suggesting epigenetic resilience linked to negligible senescence. While methylation predicts age during early years, it ceases thereafter, and regeneration events rejuvenate tissues, shedding light on their remarkable longevity and regeneration abilities. This offers molecular insights into ageing stability and tissue renewal.

September 2024 – BioRxiv

 

Key takeaways

 

  • Axolotls exhibit negligible senescence, maintaining epigenetic stability throughout most of their lifespan: Unlike mammals and many other species, axolotls’ DNA methylation – a marker of biological ageing – remains remarkably stable beyond early life. This stability suggests that axolotls avoid the molecular hallmarks of ageing seen in other organisms, offering valuable insights into the potential for epigenetic resilience and longevity in living systems
  • Age-related epigenetic changes occur only during the early years of life: Axolotls show predictable DNA methylation changes during their early years, similar to patterns observed in other species. However, these changes plateau after four years, marking a clear divergence from typical ageing processes. This unique biphasic nature of their epigenetic clock highlights a period of early development followed by a stabilised molecular state, which could underpin their exceptional longevity
  • Regeneration in axolotls involves epigenetic rejuvenation: When axolotls regenerate limbs, the tissues exhibit a ‘younger’ epigenetic age compared to non-regenerated counterparts. This rejuvenation process is particularly notable in limbs, where cells undergo dedifferentiation and reprogramming. These findings point to a potential link between regeneration and reversing molecular signs of ageing, offering clues for future therapies aimed at tissue repair and longevity

 

In other species, DNA methylation tends to increase at Polycomb Repressive Complex 2 (PRC2) target sites – a key ageing hallmark. Axolotls, however, show minimal methylation gains in these regions, even as they age. This resistance to methylation changes may help explain their prolonged healthspan and defiance of age-associated decline, serving as a blueprint for understanding molecular ageing mechanisms.

 

Read the article at: Haluza, Yuliia, et al. “Axolotl Epigenetic Clocks Offer Insights into the Nature of Negligible Senescence.” bioRxiv, 10 Sept. 2024, https://doi.org/10.1101/2024.09.09.611397. Note: at the time of publishing, the article above is a preprint.

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