A team led by scientists at the Department of Experimental and Health Sciences at Pompeu Fabra University (UPF) and the Institute of Evolutionary Biology (IBE), a joint UPF-CSIC centre, have shown which are the latest genetic causes of human ageing. The results are published this week in the journal Nature Ecology & Evolution.

Ageing has for a long time been a challenge for the public health system and poses evolutionary biologists with a fascinating scientific puzzle. There is no universal theory about the causes, nor is it clear what its overall impact will be on human health. Now, this study has used all the data accumulated over a decade of research on the genetic bases of complex diseases (from Parkinson’s to cancer through diabetes) to test different evolutionary theories of senescence.

To date, efforts to understand the evolutionary causes of ageing had been limited to experimental models like the fruit fly, and the findings were often contradictory. But today, the amount of data available concerning the relationship between genotype and phenotype represents an unprecedented opportunity to conduct these tests in humans. This information is available to the scientific community from large international databases such as the European Genome Phenome Archive (EGA): a joint project between the European Bioinformatics Institute (EBI, Cambridge) and the Centre for Genomic Regulation (CRG, Barcelona).

Arcadi Navarro, former ICREA research professor at UPF, has co-led the study that has examined the results of more than 3,000 studies with over 2,500 markers out of a total of 120 diseases. According to Navarro, “the power to determine whether an individual is healthy or any disease will develop during their life has increased greatly as more and more data have been collected”.

To start with, scientists have considered whether the markers for each disease have an effect on youth or old age. The distinction is important because if a mutation has harmful effects in old age, our genes will already have passed on to our offspring and natural selection cannot act.  The results of this study show that the frequency and the effect of the mutations that cause diseases in old age are greater than those that cause disease in early age. “We have found an evolutionary threshold at 40-50 years, a biologically significant age because it limits the reproductive period”, says Navarro.

The bioinformatic studies carried out by Juan Antonio Rodríguez, first author of the study, have also shown that there are mutations that are beneficial to youth but are harmful later in old age. However, “as they are positive in the reproductive period they will be favoured by natural selection and passed on to the offspring, and so it will be difficult to remove them”, explains Rodríguez.

“The physical decline in old age could be the evolutionary price we have to pay to reach the age of having children healthily”, says Elena Bosch, co-leader of the study and group leader at the IBE. For example, a drug that we give to a child can have negative effects when it is old. Conversely, it can also happen that a person that is very sickly as a child, if s/he survives, will enjoy excellent health as a senior citizen.

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To start with, scientists have considered whether the markers for each disease have an effect on youth or old age. The distinction is important because if a mutation has harmful effects in old age, our genes will already have passed on to our offspring and natural selection cannot act.  The results of this study show that the frequency and the effect of the mutations that cause diseases in old age are greater than those that cause disease in early age. “We have found an evolutionary threshold at 40-50 years, a biologically significant age because it limits the reproductive period”, says Navarro.

The bioinformatic studies carried out by Juan Antonio Rodríguez, first author of the study, have also shown that there are mutations that are beneficial to youth but are harmful later in old age. However, “as they are positive in the reproductive period they will be favoured by natural selection and passed on to the offspring, and so it will be difficult to remove them”, explains Rodríguez.

“The physical decline in old age could be the evolutionary price we have to pay to reach the age of having children healthily”, says Elena Bosch, co-leader of the study and group leader at the IBE. For example, a drug that we give to a child can have negative effects when it is old. Conversely, it can also happen that a person that is very sickly as a child, if s/he survives, will enjoy excellent health as a senior citizen.

Reference: Juan Antonio Rodríguez, Urko M. Marigorta, David A. Hughes, Nino Spataro, Elena Bosch,  Arcadi Navarro. Antagonistic pleiotropy and mutation accumulation influence human senescence and disease. Nature Ecology & Evolution, 2017.