Hot elephant testicles could hold clues to beating cancer and protect against ageing, according to a new study.
The large mammals are known for hardly ever getting the killer disease.
But now scientists believe they might have found the reason they developed this ability.
Elephant testicles don't drop - and researchers think that they developed anti-cancer genes in order to safeguard their temperature-sensitive sperm production.
They hope that the findings will lead to a new avenue of anti-cancer research into the cellular response to DNA damage in humans.
Despite a high number of cell division in an elephant's body which traditionally increase cancer risk, elephants hardly ever develop cancer.
The phenomenon known as Peto’s Paradox, was first observed by renowned Oxford epidemiologist Richard Peto, who noted that elephants and whales appear to be surprisingly resistant to the disease.
Recent scientific advancements have shown that key is the link between a genetic marker, the TP53 gene, and its protein product p53.
P53 identifies and neutralises damaged DNA during cell divisions and thus impedes the spread of mutations.
Remarkably, elephants stand out by hosting 20 copies of the TP53 gene, while all other known animals, including humans, possess only a single copy.
The latest study seeks to answer why this is so and proposes that multiple copies of the TP53 gene evolved not to beat cancer but to protect the quality of the elephant's sperm.
Professor Fritz Vollrath, Chairman of Save the Elephants, who carried out the latest research, said: “Elephants provide us with a unique system to study the evolution of a robust defence mechanism against DNA damage and explore the intricate details of the p53 complex in our own battle against cancer and ailments like ageing.
"Novel insights in this field are always important, but especially now that overheating is becoming ever more of an issue also for us humans.”
In mammals, the production of healthy sperm relies on the testes being several degrees cooler than the body temperature.
Consequently, the descent of testicles into a scrotum plays a vital role in cooling them as maturity approaches.
Elephants, however, lack the genes responsible for this descent, resulting in their testicles remaining inside their bodies even in mature bulls, subjecting them to elevated temperatures.
Due to their bulk, unfavourable surface ratio, thick skin and heat exchange mechanisms centred on blood flow in the ear flaps, an elphant's body temperature can soar to levels that are detrimental to mammalian metabolism and detrimental to healthy sperm production.
The diversification of p53 proteins also offers protective benefits against DNA damage and mutations in body cell lines, thus providing additional advantages linked to cancer and ageing, an area where p53 is well known to play a prominent role.
Prof Vollrath said of the study's theory: "It proposes that elephants initially evolved multiple copies of TP53 not to fight cancer but to protect sperm production in testicles that were increasingly temperature challenged as the animals grew in size during their evolutionary history.
"Sperm selection is a powerful driver in evolution and a bull’s reproductive success will depend critically on the quality of his spermatozoa, first by one sperm being successful in beating the competition to fertilise an egg and after that by the quality of the genes handed down to the zygote and developing offspring.
"Indeed, heat stress in spermatogenesis may well be a great opportunity for jumping genes to foster adaptations.
"Yet elephants are also rather good (it seems) at either avoiding or fighting cancers and it remains to be seen whether and how this ability is linked to the presence of many and diverse p53 isoform proteins encoded in their 20 copies of TP53 genes."
The findings were published in the journal Trends in Ecology and Evolution.
