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

Aldabra giant tortoises (<i>Aldabrachelys gigantea</i>) are exceptionally long-lived. We sequenced the genome and methylome of Jonathan, a 194-year-old Aldabra, to explore the molecular basis of his longevity. Relative to other giant tortoises (<i>A. gigantea</i> and <i>Chelonoidis abingdonii</i>), Jonathan has unique gene variants in most aging pathways. Moreover, Jonathan has substantial 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 lower-entropy regions in Jonathan's methylome were enriched for the promoters of genes involved in 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.