Jan 21, 2026
3 min read
Scientists have discovered an RNA hidden in the 'aging clock' of human sperm
Increasing fatherly age has been linked to increased health risks for the next generation, including higher risks of obesity and stillbirth.But what poses this growing risk remains unknown.
Most research on this link focuses on how the DNA in sperm changes with age.But sperm also contains other molecules, including many different molecules called RNAs.
Now, new research by Utah Health University shows that RNA sperm content goes through similar changes over time in mice and humans, which can lead to a rapid, dramatic change in mid -life.Furthermore, "old RNA" seems to change cell metabolism - which could contribute to the health risks of having children later in life.
"It's like finding a molecular clock that ticks with age in mice and humans, suggesting a fundamental, conserved molecular signature of sperm aging," said Qi Chen, Ph.D., associate professor of urology and human genetics at UT Health and one of the study's senior authors."Perhaps this gradual length change will slowly accumulate until it triggers a 'cliff' change in midlife," Chen added.
The results have been published in the journal EMBO.
The importance of RNA
Previous research in Chen's lab had demonstrated that sperm RNA can be altered by the father's environment, such as diet, and that these changes can affect the next generation.However, the types of RNA molecules that appear to be most important have been difficult to detect using standard techniques.
Chen's team developed a high-throughput RNA sequencing method, called PANDORA-seq, to "see" the previously undiscovered world of sperm RNA.
When using this new tool to analyze mice, the researchers discovered a pattern that they could not detect with traditional techniques: an abrupt and dramatic transition in sperm RNA in mice between 50 and 70 weeks of age.Beyond this "glow rock" they found what appeared to be a molecular clock.
As men age, the proportions of some sperm RNA change progressively - longer fragments become more common, while shorter fragments become less common.And when they looked at the RNA in human sperm, they found the same progressive change.
"At first glance, this finding seems counterintuitive," Chen said. "We've known for decades that as sperm age, their DNA becomes more fragmented and degraded.One might expect RNA to follow this pattern as well.But we found the opposite.in fact, the RNA of a given sperm gets longer with age."
The results suggest that these changes in RNA may have a significant impact on the health of the offspring.When the team introduced a cocktail of "old RNA" into mouse embryonic stem cells, which are biologically similar to early embryos, the cells showed changes in gene expression associated with metabolism and neurodegeneration, suggesting a mechanism by which RNA can influence the health of the next generation.
Finding invisible patterns
Researchers were only able to detect some of these changes when looking at RNA alone from the sperm head - the part of the sperm that carries its contents to the egg.The long tail of sperm contains other RNA that has so far obscured the pattern.
“This shift in rsRNA length is a unique signal specific to the sperm head. It is masked by the sperm's overall 'noisier' profile,” explains co-author Tong Zhou, Ph.D., assistant professor of physiology and cell biology at the University of Nevada, Reno School of Medicine and one of the paper's senior authors. “Sequencing the sperm head samples is what made this discovery possible.”
From rodents to humans to health
The researchers were able to confirm these RNA changes in humans thanks to U Health's unique clinical and research infrastructure, which connects basic science laboratories directly with andrology resources and patients, said Kenneth Aston, Ph.D., director of the Andrology & IVF Laboratory at the University of Utah and co-senior author on the paper.
"It was exciting to confirm this finding from mice to humans," Aston said."Our sperm pool at the University of Utah made this type of cross-species validation possible."
James M., director of innovation at the University of Utah Health and author of the study."This could be an important step forward for translational andrology," said Hotling, MD.
"This discovery, made possible by PANDORA-seq, could lay the foundation for future diagnostics to help guide informed reproductive decisions and improve fertility outcomes."
The team's next steps will focus on identifying the specific enzymes responsible for the changes in RNA.
"If we can understand the enzymes leading the shift, they may become acective targets for interventions to potentially improve sperm quality in aging people," says Chen."Luck under."
Conservative changes in sperm small non-coding RNA profiles during aging in mice and humans, The EMBO Journal (2026).DOI: 10.1038/s44318-025-00687-8
Journal information: EMBO Journal
Provided by Utah Health Sciences University
