Lonesome George's genes could reveal the secrets of longevity

Lonesome George died when he was about 101 years old. He was not particularly old for a Galapagos turtle, who can live up to 150 years, and he was not particularly fat, weighing only 194 pounds compared to the standard weight of about 330 pounds his turtle parents. What makes Lonesome George interesting to study is not his physique, it's the fact that he's the last of his kind.

Giant tortoises roamed, albeit slowly, in much of the world. Atlas megalochelys wandered in the Punjab region of India and Hesperotestudo crassiscutata crossed Central America to the south of the United States. Their gigantism is not the result of their life on islands, they were also huge at the time. It's just that the only giant tortoises that survived lived on isolated land isolated by oceans in quite tropical areas of the world, where a changing climate and a rapidly expanding human population could cause them little damage.

We were too late to save George's species, Chelonoidis abingdonii, but geneticists are still trying to gather an understanding of these giants by examining Lonesome George's DNA. Although he was not exceptional, his genes are. As one of the oldest organizations on the planet, C. abingdonii and other giant tortoises are of interest to anyone who wants to understand how certain animals can live for such long periods.

That's why this international group of geneticists and biologists took samples of Lonesome George and another giant turtle species, sequenced their genes and compared them to a group of other creatures. They published their results in the journal Nature Ecology & Evolution. This comparison allows geneticists to determine which genes are present at higher rates in long-lived turtles compared to other reptiles or mammals (we call this selection positive). By researching which pieces of DNA are comparatively more common in giant tortoises, researchers can begin to determine what types of traits help animals live longer. This does not mean that one of the specific genes that they have found is "the gene to live longer", but that means that sets of genes may tend to allow a longer life.

The classic example concerns telomeres. At the end of all the DNA strands are fragments of repetitive sequences called telomeres, which act as end caps for the individual strands. We all start with very long telomeres because the cellular machinery that replicates the DNA is imperfect and can not reproduce the entire strand – a small piece at the end is cut every time. If we constantly cut down DNA fragments coding for important proteins, our cells could not function for more than a few replication cycles. Instead, we cut our telomeres, which do not encode anything. The problem, of course, is that you can not push them back and your telomeres become so short that the cell can no longer divide. This seems to make a significant contribution to the aging process, so a lot of research on aging is focused on how to slow the decline of telomeres or regenerate them after they disappear.

Giant tortoises, as this study indicates, have genetic variants in proteins that repair and maintain DNA, particularly telomeric parts. The researchers used this to indicate that telomere maintenance could play a role in the survival of these turtles for so long.

But it is perhaps more interesting to see how giant species such as Lonesome George avoid one of the wounds of our modern existence: cancer. "An important trait of large, long-lived vertebrates is their need for more stringent cancer protection mechanisms," write the authors in the article, citing a paradox called Peto's paradox.

You've probably never heard of Peto or his paradox, so let us elaborate.

Richard Peto is Professor of Medical Statistics and Epidemiology at Oxford University. He noticed that large animals do not develop cancer at higher rates than small ones. This may not seem important to you, but it's actually quite surprising, since larger animals have more cells. Cancer is simply a disease of cell division: every time a cell divides, it must replicate its DNA, and this process is subject to errors. This means that each division is on the occasion of a transfer. More divisions lead to more mutations, and more mutations increase the risk that a cell becomes cancerous. Since larger animals have more cells, it makes sense that they are more prone to cancer – they simply know more divisions. But they do not do it. Studies on body size and cancer risk show no correlation between species. Within a species, the story is different. Larger humans appear to have higher cancer rates, even after controlling for potentially confounding factors. This is not definitive proof, but it adds to the evidence. If even slightly larger humans seem to develop more cancers, much larger species must have developed ways to avoid cancer, otherwise each tortoise would die.

Turtles, despite their enormous size, almost never seem to have cancer. And indeed, when these biologists examined the genomes of the giant tortoise, they found more copies of genes known to suppress tumor formation, as well as duplications of other genes that could help the immune system identify and to kill potential cancer cells. All of these changes are minor in themselves, but together they suggest that giant tortoises are generally better able to avoid cancer.

We will not go into all the other individual conclusions of this article because they contain a ton, most of which are incredibly detailed and esoteric. Turtles appear to have a slower metabolism, for example, which some scientists believe could help slow aging. They also have mutations that can help them better regulate glucose uptake and resist hypoxia. All research will require more research to determine exactly which genes contribute to a longer life and how – this research is just the first step. Much remains to be done before these discoveries help us to stay young – or, more urgently, to save other species of Galapagos turtles. For the moment, it's good to know that Lonesome George could help us better understand his family, even after he leaves. It may have been the last C. abingdoniibut he was the first in our hearts.