Analysis of genomic and behavioral data from the massive UK Biobank conclusively demonstrates that genes that promote reproductive behavior come at an ultimate cost. Aging is undoubtedly painful. There will be marks on your skin, your movements will be sluggish, you will forget things, everything will hurt you. Your joints crack and pop. How can we still endure aging when evolution has accomplished so many amazing things?
The antagonistic pleiotropy hypothesis suggests that as you age, your body breaks down to pay the price of being more fertile in your youth. If the same gene has different effects at different times of life (called pleiotropy) -- if it improves your chances of reproducing when you're young, but has harmful effects on you in some way once you get older -- then the gene will still undergo positive selection and remain in the population because reproduction is so important.
The idea is appealing, and there is some anecdotal evidence, but it's difficult to prove definitively genetically -- especially since reproductive traits and lifespan are heavily influenced by environmental factors and life choices as well as genes. However, the UK Biodatabase makes this proof possible.
The UK Biobank holds the complete genomes of 500,000 British volunteers aged between 40 and 70. The genomes were checked against information such as the individual's blood pressure, heart rate, grip strength, bone density, arterial stiffness, vision, height, weight, hip and waist circumference, workplace, education, employment and medical history, diet and exercise habits, smoking and drinking status. Volunteer recruitment took place from 2006 to 2010, and information collection continued until 2016. Researchers around the world can access this information.
One of the researchers is Zhang Jianzhi, whose lab website declares he is "most interested in the relative roles of chance and necessity in evolution." He used data from the UK Biobank to try to answer the following question: Are genetic variants that affect reproduction more likely to affect lifespan than expected by chance? If so, is this association antagonistic? Are these mutations that both promote reproduction and cause aging favored by natural selection? The answer is yes, yes, yes.
Reproductive fitness doesn't just mean how many children you have. To assess this, the researchers also looked at genes associated with reproductive activities, such as age at having your first child (oddly, this was only for women), age at first sexual intercourse, and age at menarche and menopause. Since most of the people in the UK Biobank were still alive, the researchers tested the genetic correlation of these factors with their parents' longevity. Since they knew how many siblings each participant had, they could also look for correlations between parents' reproductive potential and lifespan.
Most loci mediating the high reproductive rate/short lifespan correlation are located in noncoding regions of genes. This means they don't change the proteins the genes make; instead, they change the timing and type of cells in which those proteins are made. For example, one genetic variant is associated with younger age at first intercourse and an increased risk of melanoma and lung cancer later in life.
These genetic factors run counter to environmental influences that have led to declining birth rates and increased life expectancy since the middle of the last century. The authors note that increased lifespan is part of the reason they found evidence of antagonistic pleiotropy in their genomic data.
Therefore, the greater the reproductive capacity, the shorter the life span. It's not because your kids will drive you crazy and spend all your money, although they probably will. That's just the cost of having children.
Reference: Science Advances, 2023. DOI:10.1126/sciadv.adh4990