Analysis of genomic and behavioral data from the vast UK Biobank finally demonstrates that genes that promote reproductive behaviors come with the ultimate price.

Aging stinks. You get marks on your skin, you’re slower, you forget stuff, and everything hurts. Your joints crack and pop. Evolution has achieved so many remarkable things; how is it possible that we still have to put up with growing old?

The antagonistic pleiotropy hypothesis states that your body falls apart when you’re old to pay the cost of being reproductively fit when you’re young. If the same gene has different effects (called pleiotropy) at different times of life—if it enhances your chances of reproduction when you’re young but is deleterious somehow once you get older—that gene will still undergo positive selection and remain in the population because reproduction is that important.

It’s an appealing idea, and there is some anecdotal evidence for it, but it has been very difficult to definitively demonstrate genetically—especially because both reproductive traits and life span are very much impacted by environmental factors and life choices, as well as by genes. But the UK Biobank has made that demonstration possible.

“An unprecedented opportunity”

The UK Biobank has the complete genomes of half a million British volunteers between the ages of 40 and 70. Those genomes are collated with the individuals’ blood pressure, heart rate, grip strength, bone density, arterial stiffness, vision, height, weight, hip and waist measurements, location, education level, employment and medical histories, diet and exercise habits, smoking and drinking status, etc. Volunteers were recruited between 2006 and 2010, and information was collected until 2016. And all of it is accessible to approved researchers around the globe.

One of those researchers is Jianzhi Zhang, whose laboratory website proclaims that "the Zhang lab is most interested in the relative roles of chance and necessity in evolution.” He used the data in the UK Biobank to try to answer the following question: Are genetic variants that influence reproduction more likely to affect life span than would be expected by chance? If so, is this association antagonistic? And are these variants that promote reproduction but also cause aging favored by natural selection? The answers are yes, yes, and yes.

Reproductive fitness doesn’t mean only the number of kids you have. To assess it, the researchers also looked at the genes associated with reproductive activities like your age when you had your first child (weirdly, this was only noted for women), the age at which you first had sex, and the age of menarche and menopause. Since most of the people in the UK Biobank are still alive, researchers tested the genetic correlation of these things with their parents’ life spans. Since they know how many siblings each participant has, they could also look for correlations between the parents’ reproduction and life span.

Genes vs. environment

Most of the genetic sites that mediate the correlation of high reproduction/shorter life span occurred in non-coding regions of genes. This means they don’t change the proteins that are made by the genes; instead, they change when and in which cell types those proteins are made. One genetic variant, for example, is associated with younger age at first intercourse and also with an increased risk of melanoma and lung cancer later in life.

These genetic factors run counter to environmental effects, which have led to declining birth rates along with increased life expectancies since the middle of the last century. The authors note that these extended life spans are part of what enabled them to find evidence for antagonistic pleiotropy in the genomic data.

So, the more reproductive you are, the shorter your life span will be. Not because your kids will drive you crazy and spend all of your money, although they will likely do that. It's just the price you pay for having them.

Science Advances, 2023.  DOI:  10.1126/sciadv.adh4990