Renowned for their regenerative abilities, axolotls also exhibit exceptional longevity, resistance to age-related diseases and apparent lack of physiological declines through lifespan, and have thus been considered organisms of negligible senescence. Whether axolotls display epigenetic hallmarks of ageing remains unknown. Here, we probe the axolotl DNA methylome throughout lifespan and present its first epigenetic clocks. Both at tissue-specific or pan-tissue levels, the clocks are biphasic, capable of predicting age during early life but not for the rest of its lifespan. We show that axolotls exhibit evolutionarily conserved features of epigenetic ageing during early life, yet their methylome is remarkably stable across lifespan, including at Polycomb Repressive Complex 2 (PRC2) target sites, suggesting that this species deviates from known patterns of epigenetic ageing. This study provides molecular insights into negligible senescence and furthers our understanding of ageing dynamics in animals capable of extreme regeneration.
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Axolotls’ Epigenetic Clocks Stop Ticking
Even regenerating limbs makes the area epigenetically younger.
Ever wished you could hit the pause button on ageing? At least one creature may do just that. Axolotls seem to halt one of the hallmarks of the process part way through their lives, a finding that could shed new light on ageing and regeneration.
Axolotls (Ambystoma mexicanum) belong to a group of amphibians called salamanders, which are famed for their astonishing powers of regeneration, such as regrowing amputated limbs. They also appear to age very little, a feature called negligible senescence.
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