Genetic mutations that promote reproduction tend to shorten human lifespan, study finds

A University of Michigan study based on an examination of the genetic and health information of more than 276,000 people finds strong support for a decades-old evolutionary theory that sought to explain aging and senescence.

In 1957, evolutionary biologist George Williams proposed that genetic mutations that contribute to aging could be favored by natural selection if they are advantageous early in life by favoring earlier reproduction or the production of greater numbers of offspring . Williams was then an assistant professor at Michigan State University.

Williams’ idea, now known as the pleiotropic antagonist theory of aging, remains the dominant evolutionary explanation for senescence, the process of aging or aging. Although the theory is supported by individual case studies, it lacks unambiguous genome-wide evidence.

In the study published in Scientists progressUM evolutionary biologist Jianzhi Zhang and a Chinese colleague tested Williams’ hypothesis using genetic, reproductive and death record information from 276,406 participants in the UK’s Biobank database.

They found that reproduction and lifespan were strongly negatively correlated genetically, meaning that genetic mutations that favor reproduction tend to shorten lifespan.

Additionally, according to the study, individuals carrying mutations that predispose them to relatively high reproductive rates have lower probabilities of living to age 76 than those carrying mutations that predispose them to relatively low reproductive rates. .

However, the authors caution that reproduction and lifespan are affected by both genes and the environment. And compared to environmental factors – including the impacts of contraception and abortion on reproduction and medical advances on lifespan – the genetic factors discussed in the study play a relatively minor role, according to the authors.

“These results strongly support Williams’ hypothesis that aging is a byproduct of natural selection for earlier and greater reproduction. Natural selection cares little about how long we live after reproduction ends , because our fitness is largely defined at the end of the reproductive period. reproduction,” said Zhang, the Marshall W. Nirenberg Collegiate Professor in the U-M Department of Ecology and Evolutionary Biology.

Fitness is a concept that biologists use to describe the degree to which an organism’s characteristics increase the number of its offspring.

“Interestingly, we found that when taking into account the genetically predicted quantity and timing of reproduction, having two children corresponds to the longest lifespan,” Zhang said. “Having fewer or more children reduces lifespan.” This result confirms the conclusions of several previous studies.

Zhang’s co-author on the Scientists progress The article is Erping Long of the Chinese Academy of Medical Sciences and Peking Union Medical College. Long was a visiting student at UM when the study began.

In genetics, the concept of pleiotropy postulates that a single mutation can influence several traits. The idea that the same mutation can be both beneficial and harmful, depending on the situation, is known as antagonistic pleiotropy and was proposed by Williams to explain the origin of aging in a paper titled “Pleiotropy, Selection natural and evolution of senescence. “

To a biologist, senescence specifically refers to a gradual decline in bodily functions that manifests as a decline in reproductive performance and an increase in mortality rate with age.

The UK Biobank database allowed Zhang and Long to assess the genetic relationship between reproduction and lifespan on a genomic scale.

The researchers examined the frequency of 583 genetic variants associated with reproduction in the database and found that several of the variants associated with higher reproduction have become more common in recent decades, despite their simultaneous associations with longer life span. shorter life. The increased frequency of variants is likely the result of natural selection toward higher reproduction.

“The antagonistic pleiotropy hypothesis predicts that most mutations that increase reproduction but reduce lifespan have greater fitness advantages than disadvantages and are therefore selectively favored,” Zhang said.

Yet human life expectancy, birth rates, and reproductive behavior have all changed dramatically in recent decades. Specifically, more than half of humans live in areas of the world where birth rates have declined, alongside increased incidences of contraception, abortion and reproductive disorders, according to the new study.

In contrast, global human life expectancy at birth has increased steadily, from 46.5 years in 1950 to 72.8 years in 2019.

“These trends are mainly driven by substantial environmental changes, including changes in lifestyles and technologies, and are opposed to changes caused by natural selection of the genetic variants identified in this study,” Zhang said.

“This contrast indicates that, compared to environmental factors, genetic factors play a minor role in the human phenotypic changes studied here.”