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

Aldabra giant tortoises (Aldabrachelys gigantea) are exceptionally long-lived. We sequenced the genome and methylome of Jonathan, a 192-year-old Aldabra, to explore the molecular basis of his longevity. Relative to other giant tortoises (Aldabrachelys gigantea and Chelonoidis abingdonii), Jonathan has unique gene variants in most aging pathways. Moreover, Jonathan has significant DNA methylation and methylation entropy changes, compared to four other Aldabras ranging in age from a 5-year-old juvenile to older adults. Notably, we found that low entropy regions in Jonathan’s methylome were enriched for the promoters of genes involved in DNA repair, the mitochondrial electron transport chain, and RNA metabolism. This suggests that high-fidelity transcription of the genes in these pathways may be crucial for long-lived species. Our findings support a model for aging wherein the maintenance of low methylation entropy in gene promoters is coupled to efficient mitochondrial energy production, efficient RNA processing, and efficient genomic repair. Teaser: