Study Shows Aged Sperm RNA Alters Cellular Metabolism in Offspring - Video

As more people choose to start families later in life, scientists are racing to understand how a father’s age might quietly shape the health of the next generation. A new study now suggests that the answer may lie not just in DNA, but in a lesser-known molecular messenger carried by sperm: RNA.

RNA plays a critical role in regulating how genes are switched on and off, especially during early development. In this study, published in The EMBO Journal, scientists used a newly developed sequencing technique called PANDORA-seq, designed to detect types of sperm RNA that standard methods often miss. This advanced approach allowed them to observe patterns that had remained invisible until now.

For years, research has shown that increasing paternal age is linked to higher risks in children, including obesity, metabolic disorders, and even stillbirth. Until now, most explanations focused on age-related damage to sperm DNA. But researchers at the University of Utah Health have uncovered a new layer to this story, revealing that sperm RNA changes dramatically with age, and in surprisingly similar ways in both mice and humans.

When the team analyzed mouse sperm, they found a striking “aging cliff”—a rapid shift in RNA composition occurring at mid-life. Alongside this sudden transition, they identified what appears to be a molecular clock: as males age, certain sperm RNAs gradually become longer, while shorter RNA fragments decline. When researchers examined human sperm, they found the same progressive lengthening pattern, suggesting a conserved biological process across species.

This discovery was unexpected. While aging is known to fragment sperm DNA, the researchers found that specific RNAs actually grow longer over time. Importantly, these changes were most clearly seen in the sperm head—the part that enters the egg—highlighting their potential relevance for offspring development.

To explore possible consequences, the team introduced “old” sperm RNA into mouse embryonic stem cells. The cells showed altered gene activity linked to metabolism and neurodegeneration, offering a possible explanation for how paternal age might influence long-term health outcomes in children.

In the future, understanding and potentially targeting these RNA changes could lead to better diagnostics, improved fertility counseling, and healthier outcomes for families—no matter when parenthood begins.

REFERENCE: Shi, J., et al. (2026). Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging. The EMBO Journal. DOI: 10.1038/s44318-025-00687-8. https://link.springer.com/article/10.1038/s44318-025-00687-8.