Genetic variants linked with promoting early reproductive health have been associated with shorter lifespan, aligning with an evolutionary theory of ageing dating back to 1957.

Researchers at the University of Michigan analysed 583 reproduction-associated genetic variants in over 276,000 people from the UK Biobank, and found that individuals with these mutations were less likely to live until 76. While the effects of these variants are small in comparison to life-extending environmental and societal factors, these results align with a theory of ageing proposed by the evolutionary biologist George Williams, who suggested that mutations which may be harmful later in life could be still be evolutionarily advantageous if they promote early reproductive fitness.

'These results provide strong support for the Williams hypothesis that ageing arises as a byproduct of natural selection for earlier and more reproduction', said Jianzhi Zhang, professor of evolutionary biology from the University of Michigan, who led the study. He added, 'Natural selection cares little about how long we live after the completion of reproduction, because our fitness is largely set by the end of reproduction.'

The theory proposed by Williams, which is now known as the antagonistic pleiotropy theory, was developed in order to make sense of why we age. While this pattern has been observed in individual cases and experimental studies, the specific genomic features had not yet been observed on a large scale.

The researchers were able to estimate the overall reproductive health of individuals within the UK Biobank study by using associated genetic variants to create a polygenic score, which could be compared with matched lifespan data. Some of these variants associated with improved reproductive health have also been linked with increased disease risks, offering a potential mechanism explaining these patterns.

However, the authors note that the contributions of these genetic variants is relatively small compared with factors such as medical advances and availability of contraception, which have led to reduced birth rates and improved overall survival.

'These trends are primarily driven by substantial environmental shifts, including changes in lifestyles and technologies, and are opposite to the changes caused by natural selection of the genetic variants identified in this study', said Professor Zhang, who also told New Scientist, 'these changes have been extremely impactful, such that genetic changes are minute compared to environmental factors.'

Future research may focus on determining whether this pattern is also observed in a range of groups, including Asian and African populations, who are less represented within the UK Biobank cohort.

However, the influence of this study has still been considered substantial, with Professor Steven Austad of the University of Alabama at Birmingham describing the results in New Scientist as the 'first strong evidence of antagonistic pleiotropy in humans, supporting a major pillar of evolutionary ageing theory'.

These results have been published in the journal Science Advances.