Mammalian Evolution Reveals 2,000 New Key Genes for Human Longevity
What determines the Life expectancy of each species? This is a fundamental and very complex question that has aroused curiosity in the scientific field throughout history. From an evolutionary point of view, the main cause of these differences between species lies in their ecological adaptations.
There are long-lived species like whales that can live up to 200 years
For example, life expectancy is longer in species adapted to living in trees, underground or with high body mass, since all these adaptations reduce mortality from predation.
In the case of mammals, these present a huge variation, ranging from short-lived species such as the shrews and the mice, which hopefully reach two years of life, to long-lived species such as the Whales, which can live up to 200 years.
As for the humansWe can potentially live 120 years, and on average we are all very long-lived. The keys to our long life expectancy, however, are still largely unknown.
So far, most studies have looked for human longevity genes by comparing genomes within our species. However, the observed mutations can only explain the moderate variability – of tens of years – in the life expectancy of modern humans, much less than the variation observed among other mammals.
Now an international research team led by researchers from the Institute of Evolutionary Biology (IBE), a center of the Higher Council for Scientific Research (CSIC) and Pompeu Fabra University (UPF), has identified more than 2,000 new genes linked to longevity in humans from an evolutionary study of comparative genomics that has included up to 57 species of mammals.
The genes detected are involved in biological mechanisms that have to do with the lengthening of life in mammals, such as DNA repair, coagulation or the inflammatory response, and encode more stable proteins in species that live longer. Taken together, the observed mutations largely reflect the variability in longevity of current human populations.
The genes detected are involved in biological mechanisms that have to do with the lengthening of life in mammals, such as DNA repair and coagulation or the inflammatory response
“When you only compare human genomes, you see differences between the genes that encode the small differences in longevity between people. But the genetic structure behind the character perhaps it is based on mutations that were fixed millions of years ago in our lineage, and that now we all have incorporated ”, he explains Arcadi Navarro, principal investigator at the Evolutionary Genomics Laboratory of the IBE and co-responsible for the study.
“Using the variation that exists between other mammalian species, you can get much closer to identifying other changes that are in the nature of longevity and that perhaps do not significantly differentiate us genetically between humans”, comments the study co-author Gerard Muntané, a researcher for Navarro’s group and also a researcher at the Pere Virgili Health Research Institute.
Protein stability at the heart of longevity
One of the effects observed in all mammals after a certain age is that the proteoma –All of the proteins expressed by the genome– is destabilized, for reasons that are not yet well understood.
Proteins that contain amino acid changes in older organisms are significantly more stable than proteins in shorter-lived organisms.
Over time, protein they become unstable, and this contributes to general physiological decline. The proteins that are destabilized in each species do so at very different ages.
As a result of this study, the research team discovered that the proteins they contain amino acid changes in older organisms, they are significantly more stable than proteins in shorter-lived organisms.
“We consider that a protein is more stable when it continues to perform its function for a longer time inside the cell without being degraded. With our approach, we have seen that this generic stabilization of the proteome is found mainly in the genes that we have detected as linked to age and longevity ”, comments Muntané.
The application of evolutionary biology to medicine
Research published in Molecular Biology and Evolution opens the door to the development of new therapeutic targets to treat aging-related diseases in humans. The results of this study demonstrate the potential of the approach to medicine from the point of view of evolution.
The perspective of evolutionary biology can make very important and directly applicable contributions to human health
“The perspective of the evolutionary biology it can make very important and directly applicable contributions to human health, despite the fact that it is often ignored as a research paradigm ”, emphasizes Navarro.
The methodology developed by the research team could be used to answer other questions related to the Human health in the future. “We could study any character of human health or disease, such as blood pressure, the cholesterol or the Cancer, following the same approach ”, concludes Muntané.
Farré X., et al. “Comparative analysis of mammal genomes unveils key genomic variability for human lifespan” Molecular Biology and Evolution, 2021
The study has received funding from the European Regional Development Fund, the State Research Agency and the Generalitat of Catalonia, among others.
The perspective of the evolutionary biology can make very important and directly applicable contributions to human health,
Source: IBE (UPF-CSIC)
Rights: Creative Commons.