Having youngsters previous in existence is genetically related to loss of life more youthful

People who are genetically predisposed to having children earlier in life are less likely to live to the age of 76, according to an analysis of more than 270,000 people’s genomes.

Why we age is one of the biggest evolutionary mysteries. The process of natural selection might suggest that people should pass on genes that are advantageous to living longer, thus having more time to reproduce, but there has been no evidence to support this.

One of the leading explanations for why is that the genetic mutations that favour reproducing earlier in life could also result in a lower lifespan – an idea called antagonistic pleiotropy.

“It’s because natural selection largely cares about reproduction,” says Jianzhi Zhang at the University of Michigan. “So those mutations that are beneficial for reproduction, but may be detrimental afterwards, would still be selected.”

After conducting the largest study on the genetic link between reproduction and lifespan to date, Zhang and Erping Long at the Chinese Academy of Medical Sciences in Beijing have now found more convincing evidence for antagonistic pleiotropy.

The pair analysed genomes from 276,406 people in the UK Biobank, a long-term health study. All the chosen participants in this study were born between 1940 and 1969 and were of European ancestry.

For each person, the researchers calculated a polygenic score, an assessment of a mix of genetic variants linked to better reproductive health in early life. The higher someone’s score, the more likely they are to be fertile for longer.

They also collected information on the participants’ lifespans – either how long they lived themselves, or how long their parents lived for those who were still alive.

By comparing the polygenic scores to the lifespan data, the pair found that people who had higher polygenic scores for reproductive health had a lower probability of living to 76 years old. There was no specific reason for using this age as a cut-off, says Zhang.

Those born earlier also tended to have a lower polygenic score than those born closer to 1969, suggesting that traits that enhance reproduction are still being selected despite their impact on longevity, says Zhang.

“Our findings are in strong support of the antagonistic pleiotropy hypothesis,” he says. One potential mechanism is that some gene variants that enhance reproductive attributes may result in disease later in life. One such variant called rs12203592, for example, has been linked to some cancers.

The team now hopes to collect further data from more diverse populations to see if this trend holds. “Whether our results apply to African or Asian people, we don’t know yet, but I think we can expect to see this pattern.”

It is also important to note that external factors, including medical advances, have been leading to people living longer and having fewer children on average. “These changes have been extremely impactful, such that genetic changes are minute compared to environmental factors,” says Zhang.

“[It is the] first strong evidence of antagonistic pleiotropy in humans, supporting a major pillar of evolutionary ageing theory,” says Steven Austad at the University of Alabama at Birmingham. “There had previously been abundant evidence in laboratory animals, but to extend to humans is important for recognising the generality of antagonistic pleiotropy.”