{"id":243002,"date":"2026-01-20T19:28:09","date_gmt":"2026-01-20T19:28:09","guid":{"rendered":"https:\/\/www.newsbeep.com\/nz\/243002\/"},"modified":"2026-01-20T19:28:09","modified_gmt":"2026-01-20T19:28:09","slug":"scientists-discover-a-hidden-rna-aging-clock-in-human-sperm-theu","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/nz\/243002\/","title":{"rendered":"Scientists discover a hidden RNA \u2018aging clock\u2019 in human sperm \u2013 @theU"},"content":{"rendered":"

Reposted from U of U Health<\/a>.<\/p>\n

Increasing paternal age has been linked to elevated health risks for the next generation, including higher risks of obesity and stillbirth. But what drives this increased risk remains unknown.<\/p>\n

Most research into this link focuses on how the DNA inside sperm changes with age. But sperm carries other molecules as well, including a diverse array of molecules called RNAs. Now, new research from University of Utah Health has shown that the RNA 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. What\u2019s more, \u201cold RNA\u201d seems to change cells\u2019 metabolism\u2014potentially contributing to the health risks of having kids later in life.<\/p>\n

\u201cIt\u2019s like finding a molecular clock that ticks with age in both mice and humans, suggesting a fundamental, conserved molecular signature of sperm aging,\u201d said\u00a0Qi Chen,<\/a> associate professor of urology and human genetics and a senior author of the research. \u201cMaybe this progressive length shift accumulates quietly, until it triggers the \u2018cliff\u2019 change at mid-life.\u201d<\/p>\n

The results are published in\u00a0The EMBO Journal.<\/a><\/p>\n

\"\"<\/a>Left to right, researchers Jiancheng Yu, Xudong Zhang and Qi Chen. Image credit: Niki Tonks \/ University of Utah Health.
\nThe Importance of RNA<\/p>\n

Previous work in Chen\u2019s lab had established that RNA in sperm could be changed by a father\u2019s environment, including diet, and that those changes could impact the next generation. But the kinds of RNA molecules that seemed to be most important were difficult to detect with standard techniques. Chen\u2019s team developed an advanced RNA sequencing method, called PANDORA-seq, to \u201csee\u201d this previously undetectable world of sperm RNAs.<\/p>\n

When they used this new tool to analyze sperm in mice, the researchers spotted a pattern that traditional techniques couldn\u2019t detect\u2014a sharp, dramatic transition in sperm RNA contents in mice between 50 and 70 weeks of age. In addition to this \u201caging cliff,\u201d they found what appeared to be a molecular clock. As males age, the proportions of certain sperm RNAs change progressively\u2014longer fragments become more common, while shorter fragments become less common. And when they looked at RNA in human sperm, they found the same progressive shift.<\/p>\n

\u201cAt first glance, this finding seems counterintuitive,\u201d Chen said. \u201cFor decades, we have known that as sperm age, their DNA becomes more fragmented and broken. One might expect RNA to follow this pattern. Instead, we found the opposite: specific sperm RNAs actually become longer with age.\u201d<\/p>\n

These changes in RNA may affect offspring health in important ways, the results suggest. When the team introduced a cocktail of \u201cold RNA\u201d into mouse embryonic stem cells, which are biologically similar to early embryos, the cells displayed changes in gene expression associated with metabolism and neurodegeneration, potentially suggesting a mechanism by which RNA could impact the health of the next generation.<\/p>\n

Finding unseen patterns<\/p>\n

The researchers were only able to detect some of these changes when they looked at RNA from the sperm head alone\u2014the part of the sperm that delivers its contents to the egg. The long tail of the sperm contains other RNA that obscured the pattern until now.<\/p>\n

\u201cThis rsRNA length shift was a unique signal, specific to the sperm heads. It was obscured by the \u2018noisier\u2019 profile of the whole sperm,\u201d explained co-corresponding author\u00a0Tong Zhou,<\/a>\u00a0associate professor of physiology and cell biology in the University of Nevada, Reno School of Medicine. \u201cSequencing the sperm head sample is what made this discovery possible.\u201d<\/p>\n

From mice to humans to health<\/p>\n

Researchers were able to confirm these RNA changes in humans thanks to U of U Health\u2019s unique clinical and research infrastructure, which connects basic science labs directly with andrology and patient resources, said\u00a0Kenneth Aston,<\/a> director of the Andrology & IVF Lab at the University of Utah and co-senior author on the paper. \u201cValidating this finding from mice to humans was really exciting,\u201d Aston said. \u201cOur sperm bank resources at the University of Utah made this cross-species validation possible.\u201d<\/p>\n

Andrology is the branch of medicine that deals with diseases specific to men.<\/p>\n

\u201cThis could be an important step for translational andrology,\u201d added co-author\u00a0James M. Hotaling,<\/a> Chief Innovation Officer at University of Utah Health. \u201cThis discovery, made possible by PANDORA-seq, could lay the groundwork for future diagnostics to help guide informed reproductive decisions and improve fertility outcomes.\u201d<\/p>\n

The team\u2019s next steps will focus on identifying the specific enzymes responsible for these changes in RNA.<\/p>\n

\u201cIf we can understand the enzymes driving this shift, they could become actionable targets for interventions to potentially improve sperm quality in aging males,\u201d Chen said. \u201cStay tuned.\u201d<\/p>\n

###<\/p>\n

The study, titled \u201cConserved shifts in sperm small non-coding RNA profiles during mouse and human aging<\/a>,\u201d was published Jan. 20 in The EMBO Journal. Chen, Zhou, Aston and Hotaling were joined in the research by scientists at other institutions, including Harvard Medical School, Scripps Research Institute, University of California, Riverside and Brigham Young University.<\/p>\n

The research was funded by the National Institutes of Health, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Environmental Health Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Cancer Institute, as well as a Center for Genomic Medicine Pilot Award and Induction Bio<\/a>, a Utah biotech firm. This work includes data generated at the University of California, San Diego IGM Genomics Center. Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.<\/p>\n

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