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Science7 publishersAlso reported elsewhere3 min readPublished

Sequencing of 194-year-old Jonathan the tortoise turns up 287 gene changes unique to him

Kallel-led researchers found 287 gene changes unique to Jonathan, the 194-year-old Aldabra tortoise, touching DNA repair, inflammation, insulin and cancer. Because the baseline was just four other tortoises, the 287 are candidates to explain his slow ageing.

The Scientist · Science desk

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Photograph accompanying Sequencing of 194-year-old Jonathan the tortoise turns up 287 gene changes unique to him
Photo: newscientist.com

What happened

  • Of the 287, 41 are thought to be functionally significant, and 12 also appear in ageing databases built from other long-lived species.
  • St Helena authorities refused to let researchers draw Jonathan's blood, citing his fame and infection risk, so his genome came from saliva and cheek swabs.
  • In the first epigenome study of a giant tortoise, switches on Jonathan's DNA repair and metabolism genes closely matched those of younger tortoises.
  • Senior author Stephen Clark said regions of the genome tied to mitochondrial function look as young as those of a 5-year-old Aldabra tortoise.

Compiled by The ScientistSomething wrong?How this is made

Why it matters

  • constraint Any of the 287 could be ordinary individual variation until more Aldabra tortoises are sequenced the same way, so none can yet be ranked as a longevity factor.
  • contradiction Phys.org's account says the 287 variants reduce the effects of ageing, yet only about 14% are thought functionally significant, a far narrower claim than the headline count.
  • capability A first giant-tortoise epigenome gives later studies a reference for testing whether stable gene switches track long life in other old tortoises.
  • decision Backing Kallel's push toward human treatments means accepting Clark's view that ageing mechanisms carry across species, supported here by database matches and resemblance to supercentenarians.

The 287 is a count of differences from a small comparison group. "We found 287 genes that had changes in them that were unique to him," Clark told New Scientist, describing a comparison of Jonathan's genome with those of four other Aldabra tortoises [6][5]. Kousuke Hashimoto of the University of Osaka called the work "fascinating" [15]. He also noted, according to New Scientist, that the comparison animals were few and may have unique genetic changes of their own [15]. The coverage does not report how many unique changes each of those four tortoises showed against the others.

The researchers attribute Jonathan's long life less to good genes alone than to a lack of genetic wear and tear [21]. Phys.org's account of the Science Advances paper says the variants reduce the usual effects of aging and sit in DNA repair, inflammation control, insulin regulation and cancer suppression [2][3]. A spread across that many pathways fits the wear-and-tear description. The filtered numbers are much smaller. The 41 functional candidates are about 14% of the 287, and the dozen database matches are about 4% [7][23][24]. On the evidence published so far, the 287 are a list of candidates.

Working from saliva had costs. Without blood, the team could not isolate the large pieces of DNA that blood keeps stable; saliva DNA is more prone to bacterial contamination, and gaps in the assembly were filled with DNA from another Aldabra tortoise [9]. New Scientist calls this a major limitation [9].

"We found that the gene regulators involved in energy production and DNA repair have remained incredibly stable in Jonathan over almost two centuries," said Justin Gerlach of the University of Cambridge, a co-author [11]. The thing this doesn't tell you is which causes which. Young-looking switches in a 194-year-old animal [1] fit the idea that stable regulation helped him last. They fit just as well if stable regulation is simply what a body that stayed healthy looks like, and one tortoise cannot separate the two.

Clark links the young-looking mitochondrial regions to DNA repair. "This, in turn, has helped him manage the effects of ageing by giving the DNA repair systems more energy from the mitochondria to fight off the effects of ageing," he said [13]. The hypothesis came before the tortoise data. Manel Esteller's study of a 117-year-old woman found exceptionally efficient mitochondria, and that led Clark's team to suspect Jonathan's were similar [14].

Jonathan's age is itself an estimate. He reached St Helena in 1882 as an adult already thought to be about 50 [17]; add 144 years on the island and the total is about 194 [20][26]. The researchers put the species' average lifespan at around 80 years, so he has lived roughly 2.4 times as long [16][25].

Clark, who founded Kallel, the US nonprofit that led the work, is the study's senior author [4]. "Our goal is to take these evolutionary insights and immediately translate them into practical, affordable treatments for everyday people," he said [19]. His case for moving from tortoise to human rests on overlap, since some of Jonathan's changes resemble those found in supercentenarians [18]. "This study adds to the body of evidence that the mechanisms of ageing may be conserved across species," he said [22].

What to watch

  • Whether the team sequences a larger panel of Aldabra tortoises, showing how many private changes an ordinary animal carries against four relatives.
  • Whether St Helena authorities permit a blood sample, allowing a genome for Jonathan without gaps filled from another tortoise.
  • Whether Kallel names any of the 41 functionally significant genes as a target for human treatment work.
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