ArticleThe EMBO journal2026
Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging.
Article in The EMBO journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- A modular class-aware workflow for small RNA sequencing analysis using mouse sperm as a case study.Epigenomics · 2026Article
- Sperm 28S ribosomal RNA fragments as a potential biomarker for embryo quality in in vitro fertilization.Journal of assisted reproduction and genetics · 2026Article
- tRNA-derived small RNAs in ocular neovascular diseases: A systematic review.Non-coding RNA research · 2026Review
- qMAP decodes RNA fragmentation dynamics in development and disease.Molecular systems biology · 2026Article
- Biological aging clocks in health and disease.Nature medicine · 2026Review
- When sperm age, their RNA code hits a cliff.The EMBO journal · 2026Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
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 during aging remain ill-defined. Here, we profiled sperm small non-coding RNAs (sncRNAs) using PANDORA-seq, which overcomes RNA modification-induced detection bias to capture previously undetectable sncRNA species associated with mouse and human spermatozoa throughout the lifespan. We identified an "aging cliff" in mouse sperm RNA profiles-a sharp age-specific transition marked by significant shifts in genomic and mitochondrial tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs). Notably, rsRNAs in mouse sperm heads exhibited a transformative length shift, with longer rsRNAs increasing and shorter ones decreasing with age, suggesting altered biogenesis or processing with age. Remarkably, this sperm head-specific shift in rsRNA length was consistently observed in two independent human aging cohorts. Moreover, transfecting a combination of tsRNAs and rsRNAs resembling the RNA species in aged sperm was able to induce transcriptomic changes in mouse embryonic stem cells, impacting metabolism and neurodegeneration pathways, mirroring the phenotypes observed in offspring fathered by aged sperm. These findings provide novel insights into longitudinal dynamics of sncRNAs during sperm aging, highlighting an rsRNA length shift conserved in mice and humans.
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Registered trials
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