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These 25 Mutations Could Help Explain How Humans Have Evolved to Live So Long

MIKE MCRAE
5 SEP 2018

As far as primate life spans go, we humans have a pretty high ceiling. By some estimates, there could be as many as nearly half a million centenarians worldwide.

The discovery of just over two dozen genetic changes could go some way to help explain this ability to outlive our nearest relatives, and might even point the way to treatments that help us squeeze out a few more years in better health.

 

Researchers typically study the genetics of ageing by comparing groups of short-lived organisms, such as fruit flies or nematodes.

Occasionally, they might even take a close look at families that have more than the average number of great-grandparents showing up at family reunions, or trawl through databases to watch how genes evolve.

These all provide us with clues on which genes contribute to longer lives, but don't tell us much about why our species can live longer than a century, while our close cousins, the gorilla and chimpanzee, would do well to see their 60th birthday.

Maximum life spans in animals seem to evolve pretty quickly. The ancestors of humans and macaques, for instance, went separate ways around 30 million years ago. But there's a three-fold difference in how long we can each live.

The 'rate of living' theory might go some way to explain some differences in the animal kingdom, linking metabolic rates with the risks of cellular senescence.

Accumulations of mutations might weigh down some species, making ageing an unnecessary cost once sufficient reproduction has been achieved.

 

Another concept worth exploring is called the pleiotropic hypothesis. Dating back half a century, it was proposed by American biologist George C. Williams as a way to explain how evolutionary processes might explain the differences.

This hypothesis relies on the phenomenon of pleiotropy – single genes that affect numerous physical characteristics.

If a gene helps extend an organism's overall life span, says Williams, it will be more likely to stick around if it also helps it make it to a reproductive age.

Keep in mind, these theories might not be mutually exclusive. Ageing is complex, and there's bound to be a variety of explanations.

But every hypothesis still needs supporting evidence.

So a team led by researchers from the Institute of Evolutionary Biology in Spain hunted for mutations among different primate species to see if they could learn more about the genes that give us an edge.

By identifying statistical relationships between maximum life span and other life history characteristics contributing to health and survival, the team determined just three of the primate species in their set seemed to now outlive their ancestors – humans, and two species of macaque.

 

These species served as a benchmark for comparing the primates that had evolved to live longer lives. Following an analysis of differences in various amino acid sequences, 25 genetic changes that evolved separately in each species stood out.

"This would constitute very suggestive evidence that these genes have helped to extend their lives," says senior researcher Arcadi Navarro from the Institute of Evolutionary Biology.

These genes were largely associated with cardiovascular health, including signalling factors that helped in wound healing and changes to coagulation pathways. Which comes as little surprise to the researchers.

"The results are meaningful, because a flexible and adaptable control of coagulation mechanisms are required in species that live longer," says the study's lead author Gerard Muntané, also from the Institute of Evolutionary Biology.

Not only are these mechanisms helpful in our twilight years, the same processes affect our lives in other ways and help us reach maturity in the first place, lending weight to Williams's pleiotropic hypothesis.

Adding more primate genomes to the list, and perhaps taking into account individuals within each species, might help confirm and even further explain the role these factors play in the ageing process.

Since this case focussed mostly on the protein products of genes, there could also be numerous other factors the research missed. These 25 genes aren't the whole story, not by a long shot.

But they serve as a starting point, one that could even point the way to treatments that provide longer, healthier lives not only for us humans, but for our primate cousins as well.

This research was published in Molecular Biology and Evolution.