It takes two to tango, and yet when it comes to research into human reproduction, female fertility has always taken center stage.
Today, emerging research is taking another step forward.
Sperm from older fathers may show more signs of aging than we thought, and not just due to DNA mutations.
A recent study, published in EMBO magazinereported a clear “aging cliff” in mouse sperm that had never been detected before.
This involves RNA, which helps translate instructions stored in DNA into proteins.
In mice, the mixture of small RNA fragments carried by sperm undergoes a sharp transition around midlife.
Specifically, the heads of older sperm appear to contain more long pieces of RNA molecules and fewer short pieces.
The same pattern was later confirmed in human samples, using two separate groups of donors.
This does not establish whether humans experience the same phenomenon of abrupt aging, but the parallels are worth exploring further.
“It’s like finding a molecular clock that ticks with age in mice and humans, suggesting a fundamental, conserved molecular signature of sperm aging,” says Qi Chen, a urology researcher at the University of Utah.
“Perhaps this gradual change in length builds up quietly, until it triggers the mid-life ‘cliff’ change.”
For decades, scientists have known that as sperm age, they tend to accumulate more DNA damage and genetic mutations.
This has long been used to explain why male fertility declines with age and why harmful mutations can be passed on to offspring.
But it’s not just DNA that sperm deliver to an egg. It also delivers fragments of RNA, possibly picked up in the epididymis, the canal that carries sperm out of the testes, and these may also be important for fertilization and development.
These RNA fragments could regulate early embryonic development, and some data suggest they could even pass on environmental traits to the next generation.
In older mouse sperm, the rRNA fragments appear longer.
Additionally, when researchers introduced RNA fragments resembling those from older sperm into mouse embryonic stem cells, they observed changes in the activity of genes associated with metabolism and neurodegeneration.
This suggests that age-related changes in RNA molecules in sperm could influence how genes are expressed during early development.
The findings “unveiled a new landscape of sperm aging” in mice and humans, the authors say, “heralding a new era in reproductive health where a deeper understanding of the ‘sperm RNA code’ helps shape healthier generations.”
Noriko Osumi, a developmental neuroscientist at Japan’s Tohoku University, was not involved in the research, but in an accompanying article for EMBO magazineshe explains why sperm RNA is a “particularly interesting” target for male fertility research.
“Sperm provide more than a haploid genome,” she writes.
They also deliver fragments of RNA, which are “not simply passive remains but part of the information delivered during fertilization”. For example, they may contain epigenetic information that may influence the development of offspring.
Today, in many parts of the world, parents are having children later in life, yet scientists know very little about the aging of male sexual organs and its impact on reproduction or the health of future offspring.
A large World Health Organization (WHO) study of 8,500 couples in 25 countries found that male factors contributed entirely or at least partly to 45% of infertility cases.
In 2024, an editorial on male infertility in the journal Nature Reviews Urology argued that “the burden of male infertility is often unrecognized and its causes poorly understood.”
This means that “men may be sidelined during treatment and the burden of assisted reproductive technologies falls on the woman, even if she herself has no reproductive problems,” the editorial explains.
This new research aims to better understand how sperm function can decline with age.
Chen and his colleagues now want to understand why these RNA changes occur and how to fix them.
“If we can understand the enzymes driving this change, they could become actionable targets for interventions to potentially improve sperm quality in aging men,” says Chen.
“Stay tuned.”
The research was published in EMBO magazine.
This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. Although we are proud of our process, we are only human. If you spot an error, please let us know.
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