Scientists at University of Utah Health report a previously hidden RNA “aging clock” in sperm and propose it as a molecular mechanism linking paternal age to risks in the next generation. Chen’s team developed PANDORA-seq to detect RNAs that standard sequencing misses, and they found a reproducible pattern of age-related RNA change in mice and humans.
In mice the researchers observed a sharp transition in sperm RNA composition between 50 and 70 weeks, described as an “aging cliff.” They also found a progressive molecular clock: specific sperm RNAs become longer with age while shorter fragments decline. This pattern was mirrored in human sperm, which made the cross-species validation particularly notable.
Functionally, the team introduced a cocktail of “old RNA” into mouse embryonic stem cells, which model early embryos. Those cells showed altered gene expression tied to metabolism and neurodegeneration, suggesting one route by which sperm RNA could influence offspring health. The rsRNA length shift was detected only in the sperm head, the compartment that delivers content to the egg, and was obscured in whole-sperm profiles.
- The results are published in The EMBO Journal.
- Collaborators include researchers from Harvard Medical School, Scripps Research Institute, UC Riverside and Brigham Young University.
- Funding came from multiple NIH institutes, a Center for Genomic Medicine Pilot Award and Induction Bio.
- Data were generated at the UC San Diego IGM Genomics Center.
The team plans to identify enzymes that drive the RNA shift, which could become targets for interventions to improve sperm quality in aging males. Several researchers described the cross-species validation as an important step toward translational andrology.
Difficult words
- mechanism — a process that causes a biological change
- reproducible — able to be repeated with similar results
- transition — a change from one state to another
- fragment — a small piece of a larger moleculefragments
- embryonic stem cell — a cell that models early embryo developmentembryonic stem cells
- gene expression — process by which genes make proteins or products
- neurodegeneration — progressive loss of nerve cell structure or function
- intervention — an action intended to change health outcomeinterventions
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- How could identifying the enzymes that drive the RNA shift lead to interventions for aging sperm? Give possible steps or challenges.
- What does the cross-species validation (mice and humans) suggest about using animal models to study paternal age effects?
- If interventions to improve sperm quality were developed, what ethical or social issues should researchers consider before applying them?
