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 194-year-old Aldabra, to explore the molecular basis of his longevity. Relative to other giant tortoises ( A. gigantea and Chelonoidis abingdonii ), 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.
Authors
- Steve Horvath (ORCID: https://orcid.org/0000-0002-4110-3589)
- Lars Juhl Jensen (ORCID: https://orcid.org/0000-0001-7885-715X)
- Stephen W. Clark (ORCID: https://orcid.org/0000-0003-1732-1065)
- Li‐Wei Hung (ORCID: https://orcid.org/0000-0001-6690-8458)
- Christopher D. Faulk (ORCID: https://orcid.org/0000-0002-9749-9658)
- Mathia Colwell (ORCID: https://orcid.org/0000-0001-5008-8520)
- Todd R. Robeck (ORCID: https://orcid.org/0000-0001-8573-5070)
- Daniel P. Schmitt (ORCID: https://orcid.org/0009-0002-6057-5669)
- Angela Jones (ORCID: https://orcid.org/0000-0002-1565-4360)
- Justin Gerlach (ORCID: https://orcid.org/0000-0002-0157-0449)
- Vinayak Kapatral (ORCID: https://orcid.org/0000-0002-0501-3738)
- Madison L. Taylor
- Pascal Notin (ORCID: https://orcid.org/0000-0002-1877-8983)
- Konstantin Weißenow (ORCID: https://orcid.org/0000-0002-2205-1795)
- Benjamin Vaisvil (ORCID: https://orcid.org/0000-0003-1688-0295)
- Thomas C. Terwilliger (ORCID: https://orcid.org/0000-0001-6384-0320)
- Yanjun Ma (ORCID: https://orcid.org/0000-0002-0521-8434)
- Burkhard Rost (ORCID: https://orcid.org/0000-0003-0179-8424)
- Jonathan Hollins
- James Ford
- Sam Pascucci
- Kathlyn Reed
Institutions
- University of Copenhagen (DK)
- SeaWorld Entertainment (US)
- University of Minnesota (US)
- Los Alamos National Laboratory (US)
- Harvard University (US)
- University of California, Los Angeles (US)
- Oregon Health & Science University (US)
- Vanderbilt University (US)
- University of Cambridge (GB)
- New Mexico Consortium (US)
- Epiphany Biosciences (United States) (US)
- Tennessee Oncology (US)
- St. Helena Hospital (US)
- Igenbio (United States) (US)
- Vanderbilt-Ingram Cancer Center
- Technical University of Munich (DE)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-10-07
- DOI
- https://doi.org/10.1126/sciadv.adw8887
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00