Epigenomic insights into extreme longevity in the world's oldest terrestrial animal, Jonathan

Vaisvil, B.; Schmitt, D. W.; Jones, A.; Kapatral, V.; Ford, J. M.; Taylor, M. L.; Colwell, M.; Hollins, J.; Pascucci, S.; Weissenow, K.; Rost, B.; Notin, P.; Gerlach, J.; Terwilliger, T. C.; Hung, L.-W.; Jensen, L. J.; Horvath, S.; Faulk, C.; Ma, Y.; Clark, S. W.

doi:10.1101/2025.02.05.636284

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bioRxiv · 10.1101/2025.02.05.636284

Epigenomic insights into extreme longevity in the world's oldest terrestrial animal, Jonathan

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Abstract

Giant tortoises exhibit exceptional longevity, often exceeding the human lifespan. To understand the genomic and epigenomic basis of their longevity, awe analyzed the DNA sequence and methylome of Jonathan, an Aldabra giant tortoise (Aldabrachelys gigantea), estimated to be 192 years old. Relative to other giant tortoises (Aldabrachelys gigantea and Chelonoidis abingdonii), we found Jonathan has gene variants in pathways associated with aging, including DNA repair and telomere regulation. Consistent with his advanced age, Jonathan has significant age-related changes in DNA methylation and methylation entropy, compared with a 5-year-old Aldabra individual. Notably, we found that low entropy regions in Jonathans methylome were enriched for genes involved in the electron transport chain. This suggests that high-fidelity transcription of these genes may be crucial for extreme longevity. With this data, we propose a model for aging, that links efficient mitochondrial energy production with nuclear maintenance of low methylation entropy.

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Vaisvil, B., Schmitt, D. W., Jones, A., Kapatral, V., Ford, J. M., Taylor, M. L., Colwell, M., Hollins, J., Pascucci, S., Weissenow, K., Rost, B., Notin, P., Gerlach, J., Terwilliger, T. C., Hung, L.-W., Jensen, L. J., Horvath, S., Faulk, C., Ma, Y., Clark, S. W.. 2025-02-06. Epigenomic insights into extreme longevity in the world's oldest terrestrial animal, Jonathan. https://doi.org/10.1101/2025.02.05.636284

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