Aging sperm carry DNA mistakes that get worse over time

Sperm changes with age – and not just in number or speed. As men get older, there’s a deeper shift happening in their DNA, one that affects what their children might inherit beyond eye color or height.

New research shows that as men age, their sperm carry more harmful genetic mutations. And it’s not just that DNA makes more mistakes over time. Something even stranger is happening – some of those mistakes are actually being favored during sperm production.

This means a small number of mutated sperm cells get an unfair advantage, multiplying more than their healthy neighbors. The result? Older men may have a higher chance of passing on serious genetic conditions to their children.

The research comes from the Wellcome Sanger Institute and the TwinsUK study at King’s College London, which provided access to a unique pool of DNA samples from adult twins. These samples gave scientists a rich look at how sperm mutations evolve with age in healthy individuals.

Mutations gain power within cells

Inside the testes, sperm cells are constantly renewing. Every time they divide, there’s a chance a DNA error – a mutation – slips through. Most of these are harmless. Some don’t make it far. But certain mutations give a sperm-producing cell a competitive boost, helping it outgrow the others.

It’s kind of like natural selection, but at a cellular level. This process creates little “clones” of sperm that carry the same mutation and edge out the rest. Over time, this leads to a bigger pool of sperm carrying the same potentially harmful mutation.

For a long time, scientists couldn’t measure this process accurately. The tools just weren’t precise enough. That changed with a new method called NanoSeq – an ultra-accurate way to read DNA. Using this, researchers studied sperm from 81 healthy men aged 24 to 75.

Older age, higher sperm mutation risk

The results were clear. Among men in their early 30s, about two percent of their sperm carried mutations that could cause disease. But by the time men reached their mid-40s to late 50s, that number jumped to three to five percent. And for those around 70, it reached 4.5 percent.

This isn’t just random damage adding up. The increase comes partly from how certain mutated sperm-producing cells are being selected during reproduction – a process scientists didn’t fully grasp until now.

The researchers identified 40 genes where this selective process is happening. Many of them are linked to severe neurodevelopmental disorders and inherited cancer risks in children.

While 13 of these genes had already been connected to this process, this new study shows it’s a much wider issue than previously thought.

These sperm mutations don’t always result in fertilization or healthy births. Some might prevent fertilization or lead to pregnancy loss. But the overall risk to offspring rises as more mutated sperm are produced and compete successfully.

Lifestyle shapes sperm evolution

The findings don’t just point to an increased risk with age. They also raise new questions about how environment and lifestyle could play a role in this process.

If certain conditions inside the body give mutated sperm cells an advantage, what happens when external factors – like diet, toxins, or stress – change that internal environment?

“Our findings reveal a hidden genetic risk that increases with paternal age,” said Professor Matt Hurles, Director of the Wellcome Sanger Institute.

“Some changes in DNA not only survive but thrive within the testes, meaning that fathers who conceive later in life may unknowingly have a higher risk of passing on a harmful mutation to their children.”

The rise of selfish sperm

In a separate but related study, scientists at Harvard Medical School and the Sanger Institute looked at this same issue from a different angle.

Instead of studying sperm directly, they analyzed the DNA of over 54,000 families and 800,000 individuals. They found more than 30 genes where mutations give sperm cells a competitive edge. Some of these genes overlapped with those identified in the sperm study.

That second study also uncovered something surprising. These “selfish” mutations can increase in sperm by as much as 500 times – a pattern that may explain how rare genetic diseases appear even when neither parent shows any sign of carrying them.

“We expected to find some evidence of selection shaping mutations in sperm,” said Dr. Matthew Neville, first author of the study. “What surprised us was just how much it drives up the number of sperm carrying mutations linked to serious diseases.”

Aging reshapes male fertility

This doesn’t mean older fathers should panic. Most sperm cells are still healthy. And not every mutation leads to a genetic disorder.

But it does show that the male reproductive system isn’t just passively aging – it’s changing in ways that directly affect the next generation.

“There’s a common assumption that because the germline has a low mutation rate, it is well protected,” said Dr. Raheleh Rahbari, senior author of the study. “In reality, the male germline is a dynamic environment where natural selection can favor harmful mutations, sometimes with consequences for the next generation.”

Rethinking the male biological clock

We often hear about the biological clock in women. But this research brings attention to a quieter, slower clock ticking in men. The genetic baggage passed along from father to child may get heavier with age – not just from more mutations, but from the body preferring certain harmful ones.

As scientists dig deeper, this research could open new doors for understanding fertility, genetic counseling, and maybe even personalized risk assessments based on age and lifestyle.

“This collaboration highlights the power of large, population-based cohorts for advancing our understanding of human development and inheritance,” said Professor Kerrin Small of King’s College London.

The science is still unfolding, but one thing’s clear: sperm isn’t just a carrier of genetic information. It’s a dynamic system, full of competition, change, and choices that ripple far beyond the moment of conception.

The full study was published in the journal Nature.

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