Biological age

What the DNA of Jonathan, a 194-year-old tortoise, hints about aging

Researchers read the genome of Jonathan, an Aldabra giant tortoise on St Helena thought to be about 194 years old, and compared the chemical tags on his DNA with those of four younger tortoises. The patterns look like aging in humans, with one twist the team thinks may matter. But this is mostly a study of one animal, and the authors call their model a hypothesis.

Jonathan, an Aldabra giant tortoise living on the South Atlantic island of St Helena, is considered the oldest known land animal, with an estimated age of 194 years. That is remarkable even for a giant tortoise: the paper cites an estimate that the upper limit of life expectancy for his species is about 94 years, so Jonathan has outlived it by roughly a century.

Animals that live unusually long can give clues about how aging works. Earlier studies looked at the genes of naked mole rats, bowhead whales and other tortoises, including Lonesome George, the last Galápagos tortoise of his kind. A new study in Science Advances reads Jonathan's genome and, for the first time in a giant tortoise, his epigenome: the chemical tags on DNA that help switch genes on and off.

What they did

St Helena did not allow blood to be taken from Jonathan, to avoid any risk of infection. So the team scraped cells from inside his mouth and collected saliva. Because that DNA was too broken up for some methods, they built a high-quality reference genome from the blood of Tank, a 36-year-old Aldabra tortoise living in captivity, and lined up Jonathan's DNA against it.

They then:

  • searched Jonathan's genes for signs of positive selection, changes that seem to have been favoured during evolution, and for variants that only he carries;
  • compared his genes with those of other tortoises and of long- and short-lived animals;
  • measured DNA methylation, chemical tags on DNA, in mouth cells from Jonathan and four other Aldabra tortoises: a 5-year-old, a 12-year-old and two adults whose exact age is unknown but who were already adult in 1969.

What they found

  • Variants in aging-related genes. Jonathan carries gene changes, some unique to him, in pathways linked to aging: DNA repair, the protective caps on chromosomes (telomeres), insulin signalling, the mitochondria (the cell's power plants) and cancer control. He also has 10 copies of a gene called perforin, which immune cells use to kill infected, cancerous or worn-out cells; Lonesome George had 7. Whether any of these changes actually make a difference is not known.
  • Familiar signs of age. Compared with the 5-year-old, Jonathan's DNA had fewer methylation tags overall, a pattern also seen in very old humans.
  • More disorder, except where it may count. Over time, methylation patterns tend to become more random, which can be measured as methylation entropy. Across the five tortoises, entropy rose with age, and Jonathan's was the highest. But in promoters, the stretches of DNA that switch genes on, entropy stayed low in all five.
  • A set of well-kept switches. The team found 272 gene promoters that were orderly in Jonathan and the two young tortoises but more disordered in the two older adults. Many of these genes work in the mitochondria, especially in energy production, or in handling RNA.

From this, the researchers propose a model in which keeping these gene switches orderly lets the genes for energy production, DNA repair and RNA processing work reliably, and that this helped Jonathan live so long.

What to keep in mind

  • Mostly one animal. The genome part rests on Jonathan, and the methylation comparison on five tortoises. Two of them have no known age, and Jonathan's own age is an estimate.
  • No blood, no RNA. The authors call the lack of blood their biggest limitation. It meant they couldn't use the best sequencing methods, couldn't check whether his unusual gene variants change how genes are used, and could only measure about 10% of the tortoise's promoters.
  • Predicted, not tested. The effects of Jonathan's variants were predicted with computer models, not measured in the lab.
  • A hypothesis. The authors write that their data are "insufficient to support a direct causal inference" and that more animals are needed to see whether the pattern is general.
  • Jonathan has lived a very different life from the captive tortoises he was compared with.

Why it matters

This is not a recipe for longer life, and nothing here applies directly to people. Its value is as a rare look at the DNA of an animal at the extreme end of the lifespan. The finding that the switches of energy and RNA-handling genes stay orderly in the oldest tortoise echoes studies of human centenarians, which the authors cite, and it gives researchers a specific idea to test in more long-lived animals.

Sources