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Canonical Wnt/β-catenin signalling regulates inducible aging and regeneration loss in hydra

Tökölyi, J.; Kumagai, Y.; Szilagyi, R. K.; Nagy, N. A.; Szakal, V.; Daryono, R. N. H.

2025-04-03 developmental biology
10.1101/2025.04.01.646560 bioRxiv
Show abstract

Freshwater cnidarians from the genus Hydra have exceptional regeneration capacities and show negligible aging. However, one species, Hydra oligactis, experiences accelerated senescence following sexual reproduction, characterized by regeneration loss, stem cell depletion, reduced body size, motility and food capture rates. This phenomenon, termed inducible aging, is triggered by temperature-induced sexual reproduction. The physiological regulation of the switch from high regenerative capacity and low senescence to regeneration loss and accelerated aging remain largely unexplored. By comparing gene expression patterns of asexual and sexual polyps following amputation we identified several canonical Wnt/{beta}-catenin signalling pathway transcripts that showed differential expression in the regeneration-deficient sexual individuals, suggesting the involvement of this pathway in the inducible aging phenotype. Pharmacological activation of canonical Wnt/{beta}-catenin signalling with alsterpaullone (ALP) restored head regeneration and improved survival of animals. To find out more about the role of this pathway in sexual development and post-reproductive senescence, we treated animals in various stages of egg maturation with ALP. We found that ALP delayed egg maturation when applied in early stages, but had smaller effects when applied in later stages of gametogenesis, without having a stark effect on overall fecundity. ALP treatment increased survival following sexual reproduction. These results show that the canonical Wnt/{beta}-catenin signalling pathway regulates reproduction, regeneration and post-reproductive senescence in H. oligactis.

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