Published on: Jan 20, 2026
Most studies on paternal aging focus on age-related DNA damage in sperm, but sperm also carries many other molecules, including diverse RNAs. New research from University of Utah Health reveals that sperm RNA profiles change with age in both mice and humans, following a progressive pattern that appears to culminate in a rapid shift around mid-life. This RNA “aging clock” may help explain why advanced paternal age is linked to health risks in offspring.
Using a newly developed sequencing method called PANDORA-seq, researchers were able to detect previously hidden sperm RNAs. In mice, they observed a sharp “aging cliff” between 50 and 70 weeks of age, alongside a gradual shift in RNA composition: longer RNA fragments became more common over time, while shorter ones declined. The same pattern was found in human sperm, suggesting a conserved biological process.
Surprisingly, unlike DNA which becomes more fragmented with age specific sperm RNAs actually lengthen. When “old” sperm RNA was introduced into mouse embryonic stem cells, it altered gene expression related to metabolism and neurodegeneration, pointing to a potential mechanism by which paternal age may influence offspring health.
The findings were validated in humans using the University of Utah’s integrated research and clinical resources, marking an important step toward translational andrology. Researchers say this discovery could eventually support new diagnostics or interventions to improve reproductive outcomes in aging males. The next phase of the work will focus on identifying the enzymes responsible for driving these age-related RNA changes.
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