25 genetic changes that could have extended human lifespan

Centre for Genomic Regulation (CRG)
  • A new method enables to identify 25 parallel mutations located in genes associated with wound healing, blood coagulation and cardiovascular disorders.
  • The research confirms that some genes that are beneficial in early stages of life are detrimental once the reproductive stage has ended.
  • The results could help to develop new drugs to treat ageing-related diseases.

Senescence, or biological ageing, refers to the general deterioration of an organism’s physiological functions, leading to increased susceptibility to diseases and ultimately death. A complex process that, among many other changes, involves the action of many genes.

Lifespan varies greatly across different animal species. Flies, for example, live for just four weeks, horses for close to thirty years, whereas some hedgehogs may live for up to two centuries. Why is the range of lifespans found in nature so broad? This is one of the basic and most intriguing questions faced by biologists.

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Individuals of certain species of tortoises have been known to live for up to 150 years.

Potentially, human beings could live for up to 120 years, while the species of some close primates live for only half that period. In order to explain the reasons behind these differences, researchers led by scientists at the Institute of Evolutionary Biology (IBE), in collaboration with researchers at the Centre for Genomic Regulation (CRG), the University of Bristol and the University of Liverpool, have identified genes that may have been crucial in extending the life of our species, as well as that of primates with a longer lifespan.

The genomes of seventeen primate species were studied, including humans. From the standpoint of ageing, while primates are interesting because they are very similar, there are major differences across species in terms of longevity. Of the species studied, only three ― humans and two macaques ― lived longer than the common ancestor. This proves that “they have undergone a relatively rapid process of lifespan evolution”, explains Arcadi Navarro, ICREA research professor at the IBE and the leader of the study.

ICREA research professor Toni Gabaldón and his team compared these species to those of the remaining fourteen primate species, to detect the distinctive mutations present in those with longer life expectancy. “This would constitute very suggestive evidence that these genes have helped to extend their lives”, says Navarro, who is also Professor of the UPF and CRG collaborator. Following the comparison, twenty-five mutations were identified in genes associated with wound-healing, coagulation and a large number of cardiovascular conditions.

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Of the studied species, only humans and two species of macaques have a longer lifespan than their common ancestor.

“The results are meaningful, because a flexible and adaptable control of coagulation mechanisms are required in species that live longer”, explains Gerard Muntané, the study’s leading author and a postdoctoral researcher at the IBE and at the Institut d’Investigació Sanitària Pere Virgili (IISPV). Moreover, adds Muntané, “they confirm the pleiotropy theory of ageing”. This model proposes that “certain mutations may have different effects depending on life-stage: they help us in the early stages but damage us in later stages, once the reproductive stage has ended”.

The research, published in the Molecular Biology & Evolution journal, confirms that some genes are beneficial in early stages of life, but are detrimental after the reproductive stage is finished. The authors suggest that the results could help to develop new therapeutic targets for treating ageing-related diseases and to demonstrate the potential of an evolutionary approach to medicine.

 

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