2,000 new mammal genes discovered explaining the key to human longevity

BARCELONA, Spain — What determines the lifespan of each species on Earth? For mammals, longevity varies dramatically, with some animals living for just a few years and others living for centuries! Now, a new study has discovered a collection of genes which may explain what actually determines how long we live.

A team from the Institute of Evolutionary Biology (IBE), a center of the Spanish National Research Council (CSIC), and Pompeu Fabra University (UPF) says they’ve found 2,000 new genes which have a link to longevity in humans. The results come from a review comparing the genomes of 57 different mammal species.

For humans, the average lifespan sits around 70 to 80 years and tops out around the age of 120. However, what actually determines how long someone lives on a genetic level is still a bit of a mystery. Until now, the researchers say most studies have looked specifically at human genes. Unfortunately, finding mutations just in human genes only accounts for some of the variations in the human lifespan and much less than the variations which appear in other mammals.

The key to longevity may come from the distant past

The new study reveals genes which take part in the biological processes that keep many mammal species alive. These include DNA repair, blood coagulation and inflammatory responses, and processes which arrange stable proteins in long-living species. The team discovered that most of these mutations impact the range of longevity in today’s human population.

“When you only compare human genomes, you see differences between the genes that codify small differences in longevity between people. But the genetic structure behind the character may be based on mutations that occurred millions of years ago in our lineage, and we all have incorporated now,” explains Arcadi Navarro, principal investigator at the Evolutionary Genomics Laboratory at the IBE, in a media release.

“Using the variation that exists between other species of mammals you can get much closer to identifying other changes that are in the nature of longevity that may not differentiate us significantly at the genetic level between humans,” adds study co-director Gerard Muntané.

Protein stability may reveal life expectancy

One thing the team found in all mammals is that proteome destabilizes at a certain age. This is the expression of all the proteins a mammal has in their genome. However, the reason why proteome destabilizes at some point in all animals remains unclear.

As mammals age, their proteins becomes unstable, which leads to general decline as people get older. For each species, these proteins break down at different ages. From these findings, researchers found that longer living mammals have more stable proteins containing amino acid changes in comparison to species that only live for a short time.

“We believe that a protein is more stable when it continues to perform its function longer within the cell without degradation. With our approach, we have seen that this generic stabilization of the proteome is fundamentally found in genes we have identified as being related to age and longevity,” Muntané explains.

New treatments for a longer life?

The researchers say their findings open the door to new therapies which target age-related diseases. Moreover, the results may lead to further genetic breakthroughs in the future.

“The perspective of evolutionary biology can make significant contributions and be directly applied to human health, although it is often ignored as a research paradigm,” Navarro says.

“We could study any character of human health or disease, such as blood pressure, cholesterol or cancer, following the same approach,” Muntané concludes.

The study appears in the journal Molecular Biology and Evolution.

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