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Science X / Phys.org @sciencex.bsky.social · 20/01/2026

Perhaps the most puzzling part: We see a paradox: the rsRNA length shift is progressive⏳yet the global RNA profile shows an "Aging Cliff"📉. Cliff or Progression? Maybe the gradual shift is the forerunner—accumulating silently until it triggers the cliff. bsky.app/profile/qich...

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Reposted by Qi Chen

A molecular "aging clock" has been identified in human sperm RNA, showing progressive changes with age that may influence offspring health and metabolism. doi.org/hbkmvf

phys.org

Scientists discover a hidden RNA 'aging clock' in human sperm

Increasing paternal age has been linked to elevated health risks for the next generation, including higher risks of obesity and stillbirth.

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Reposted by Qi Chen

Julie Kiefer @julieckiefer.bsky.social · 21/01/2026

Fascinating research! Qi Chen and colleagues have identified a potential "aging cliff" in sperm RNA (rsRNA) that is associated with the increased health risks for the next generation that accompany advancing paternal age. Read on uofuhealth.utah.edu/newsroom/new...

uofuhealth.utah.edu

Scientists Discover a Hidden RNA “Aging Clock” in Human Sperm

The molecular contents of sperm go through similar shifts over time in both mice and humans, which may lead to a rapid, dramatic shift at mid-life.

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Reposted by Qi Chen

The EMBO Journal @embojournal.org · 20/01/2026

What underlies the impact of sperm aging on fertility and offspring health? small ncRNA profiling by Kenneth Aston, Tong Zhou, @qichen-lab.bsky.social and colleagues reveals a drastic shift in RNA complements able to affect recipient cell metabolism link.springer.com/article/10.1...

link.springer.com

Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging - The EMBO Journal

Sperm aging impacts male fertility and offspring health, highlighting the need for reliable aging biomarkers to guide reproductive decisions. However, the molecular determinants of sperm fitness durin...

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5/5 Connecting mouse and human sperm data to uncover this conserved rsRNA length shift has been a privilege. Made possible by unique resources at @uuhsresearch.bsky.social Huge thanks to the trainees & collaborators who made this happen! @jianchengyu.bsky.social @cai000chen.bsky.social

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4/5 Crucially, beyond mouse data, we validated the sperm-head-specific rsRNA length shift signal in two independent human cohorts (longitudinal & cross-sectional). This suggests an evolutionarily conserved feature, which may stem from shared (enzymatic) mechanisms during aging.

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3/5 Perhaps the most surprising discovery: we see an age-dependent "Length Shift" in rsRNAs, exclusively found in sperm heads. Specifically, longer fragments accumulate while shorter ones decrease with age—a sign of altered RNA cleavage/processing efficiency (e.g., enzymatic).

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2/5 The first revelation: In mice, PANDORA-seq uncovers a sharp "Aging Cliff"📉in sperm RNA profiles at mid-life—a non-linear shift distinct from chronological age. Crucially, this cliff signal (genomic & mitochondrial tsRNAs/rsRNAs) is invisible to traditional small RNA-seq.

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Qi Chen @qichen-lab.bsky.social · 25/12/2025

1/5 It took us some time to connect the dots...now in @embojournal.org we use PANDORA-seq to start decoding the 'sperm RNA code of aging' We find a conserved rsRNA length shift that reflects aging in both mouse & human sperm, and an 'aging cliff' at mid-life🧵 link.springer.com/article/10.1...

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A road trip to Monument Valley and the wonders of the west, as an anniversary of lab’s 10th year operation…look forward to the journey ahead…

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Qi Chen @qichen-lab.bsky.social · 23/12/2025

Glad to see this thoughtful piece in @quantamagazine.bsky.social on paternal epigenetic inheritance and the emerging 'Sperm RNA Code', featuring many active colleagues in the field. It’s a reminder that our actions may echo in the next generation(s) & there are immense unknowns to explore...

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Reposted by Qi Chen

Bruno Di Stefano @distefanolab.bsky.social · 28/10/2025

1/ Excited to share our new study with @brumbaugh-lab.bsky.social, out in @natbiotech.nature.com! P-bodies selectively sequester RNAs encoding cell fate regulators, often from the preceding developmental stage. Releasing these RNAs can drive changes in cell identity. 🧵 www.nature.com/articles/s41...

nature.com

Selective RNA sequestration in biomolecular condensates directs cell fate transitions - Nature Biotechnology

Stem cell differentiation is controlled by manipulating RNA condensates.

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Qi Chen @qichen-lab.bsky.social · 18/09/2025

After developing PANDORA-seq to reveal hidden small RNAs (e.g., tsRNA, rsRNA) and SPORTS to annotate them, we now expand our toolchain with Tong Zhou lab: introducing FUSION, a tool that robustly interprets small RNA changes even in small or 1-on-1 datasets. academic.oup.com/bioinformati...

academic.oup.com

FUSION: a family-level integration approach for robust differential analysis of small non-coding RNAs

AbstractMotivation. Beyond well-studied microRNAs, noncanonical small non-coding RNAs (sncRNAs) derived from longer parental templates such as tRNAs, rRNAs

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Proud to work with a brave team @cai000chen.bsky.social‬ @jianchengyu.bsky.social‬ Xudong Zhang & Tong Zhou—thinking fearlessly to bring this piece together. In a time of uncertainty, may this idea be a seed for spring… We’ll see what evidence we and the community can bring, to confirm or refute…

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Beyond inheritance, the model may also apply to cancer & neurodegeneration, where abnormal RNA structures could shape pathological cell states. Perhaps misfolded RNAs — not just amyloid proteins — are the central structural entity driving disease.

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Why the memory fades eventually - as often seen in epigenetic inheritance: Two potential exits: Active reset: when conditions normalize, condensates dissolve, RBPs shift, RNA refolds. Passive fade: cells with stress-memory may grow slower, and are outcompeted over generations.

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Memory propagation in cells — and across generations: Newly folded RNAs bind stress-linked RBPs to assemble new condensates, passed on during cell division. Even daughter cells never facing the original stress can inherit the RNA structural memory – and its stress-adapted traits.

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The heart of the hypothesis: copying RNA shape. Some RNAs can act as both template & catalyst, guiding new RNAs with the same sequence to fold the same way. RNA alone is unstable, but RBPs stabilize the template, & condensates boost RNA–RNA interactions—as a microreaction chamber

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The model starts with RNA folding energy & a multistable landscape. Under stress, RNA can adopt a new shape—and if RNA-binding proteins “lock” it in, that shape becomes a molecular memory of the stress. Think Waddington’s epigenetic landscape—but for RNA folding energy valleys.

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Trends in Biochemical Sciences @cp-trendsbiochem.bsky.social · 01/05/2025

Perhaps our boldest hypothesis… we propose a model for RNA Structural Memory propagation in @natcellbio.nature.com where RNA conformation is reshaped by stress, locked by RBPs, copied prion-like in condensates & passed across generations—all without altering DNA rdcu.be/eBwPJ

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Reposted by Qi Chen

Our 🌷 May 🌷 issue is online with a broad range of article topics and formats! In their Opinion article (on the cover, too!), @qichen-lab.bsky.social and colleagues describe the interactions between small ncRNAs and Toll-like receptors. Find the issue here: www.cell.com/trends/bioch...

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Qi Chen @qichen-lab.bsky.social · 01/05/2025

Very glad to see our Sequential Activation Hypothesis highlighted on the cover @cp-trendsbiochem.bsky.social , linking small RNA-TLR interactions to autoimmune disease mechanisms.

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Qi Chen @qichen-lab.bsky.social · 04/04/2025

We put together a step-by-step protocols for PANDORA-seq, now available in Nature Protocols @natprot.bsky.social , including the sample preparation for sperm, sperm heads; and the analyzing software SPORTS optimized for various types of small RNAs including tsRNAs, rsRNAs, and miRNAs. rdcu.be/egk1Z

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Proud of @jianchengyu.bsky.social and the team for thinking fearlessly to put the ideas together!

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This idea is driven by advanced sncRNA sequencing (e.g. PANDORA-seq), uncovering an expanding universe of tsRNA/rsRNA/ysRNA & more www.nature.com/articles/s41... These sncRNAs go beyond RNAi, adopting aptamer-like roles by binding TLR7/8 to shape immune responses www.jbc.org/article/S002...

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TLR7/8 aren’t just triggered by viral RNAs, they can be potentially activated by a range of RNA resources: cell stress/death, RNA therapies, microbiome, and even dietary RNAs. Uncovering these diverse triggers may pave new paths for preventing/treating autoimmune diseases.

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