BioTechniques News
Beatrice Bowlby
After an astonishing 194 years plodding around on planet Earth, Jonathan the giant tortoise is the world’s oldest terrestrial animal – and we may finally know the secret to his extreme longevity.
Epigenetic analysis has revealed what’s kept Jonathan, the venerable giant tortoise, alive and kicking for close to two centuries. Seeking to understand the molecular basis of his remarkable lifespan, a team led by scientists from the Kallel Foundation (TN, USA) used genome and methylome sequencing to pinpoint gene variants and DNA methylation patterns that set Jonathan apart from his more youthful peers – findings that could help advance human anti-aging research.
Studying longevity in other species offers insights into extreme lifespans that could inform our own anti-aging efforts. Recent research has used comparative genomic analysis, focusing on famously enduring animals like the naked mole rat, bowhead whale and the aptly named immortal jellyfish, to deepen our understanding of gene markers that may slow aging and inhibit cancer.
Aldabra giant tortoises (Aldabrachelys gigantea) are also exceptionally long-lived – and Jonathan’s the oldest of them all. Believed to have hatched around 1832, the reptilian elder statesman is around 100 years older than the typical upper limit for his species and is considered the world’s most ancient land animal, making him an exceptional candidate for cracking the code of long life. While previous research has identified longevity-associated genetic variants in giant tortoises, no study has ever investigated the epigenetic basis of their aging, nor uncovered whether extraordinarily old individuals like Jonathan have unique epigenetic features.
At least they hadn’t, until the team from the Kallel Foundation came along and changed that. Unable to acquire blood samples due to concerns for Jonathan’s health, the researchers instead used a cheek swab and saliva samples for genomic DNA isolation and subsequent short-read sequencing. They then aligned this genome with that of Tank, a younger Aldabra giant tortoise living in captivity, to create a consensus reference genome for Jonathan and predict over 25,000 protein-coding genes.
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Comparing Jonathan’s genome to the genomes of Tank, Lonesome George – the last Pinta Island giant tortoise who lived to 100 – and humans, the scientists identified 287 genes with unique variants found only in Jonathan. Computational analyses revealed that 41 of these genes had potentially functionally significant variants, including genes involved in aging pathways such as telomerase maintenance, DNA repair, autophagy and tumor suppression.
In addition, the researchers analyzed the aged tortoise’s epigenome, performing whole-genome bisulfite sequencing on cheek DNA from Jonathan and four other Aldabras. This demonstrated that Jonathan has substantially different DNA methylation and methylation entropy compared to much younger tortoises. Most notably, promoters of genes involved in mitochondrial function and RNA processing were enriched in lower-entropy regions of Jonathan’s methylome, suggesting that high-fidelity expression of the genes in these pathways may be helping to protect Jonathan from age-related decline.
Thanks to the genetic and epigenetic insights garnered in this research, we now understand Jonathan’s incredible longevity a little better. “Nature has already solved the puzzle of aging in remarkable ways, and Jonathan’s genome provides a blueprint for cellular resilience,” commented Stephen Clark, founder of Kallel and senior author of the study.
“Our goal is to take these evolutionary insights and immediately translate them into practical, affordable treatments for everyday people.”
The post The secret to living 194 years? Ask Jonathan, the world’s oldest land animal appeared first on BioTechniques.
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