idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
idw - Informationsdienst
Wissenschaft
Some of the signs of ageing in human cells originate in the cell nucleus, because the packaged form of DNA changes with age. This has now been demonstrated by PSI researchers. It means that older cells can no longer react appropriately to external stimuli, and this can even lead to diseases. This insight could help scientists to curb such alterations and support better health in old age.
As we age, our cells age with us. Although they remain active, they become less flexible, stop dividing and sometimes respond incorrectly to signals. The reason for this lies in the cell nuclei, specifically in the chromatin – the packaged form of our DNA. This is the finding of a study by researchers at PSI, who analysed samples of skin cells taken from people of different ages in the laboratory. They have now published their findings in the scientific journal PNAS.
Using a microscope and molecular biological methods, the scientists led by G. V. Shivashankar examined how various skin cells reacted to a specific chemical messenger when mechanical tension was applied. They compared skin cells from ten-year-old children with those from 75-year-olds. As expected, the response of older people’s cells to the same stimuli was different and significantly weaker. The scientists were able to attribute this to a specific cause: the chromatin in the cell nucleus changes with age. As a result, certain genes – sections of DNA that belong together – can no longer be read as accurately. This process, known as gene expression, is important in order to produce the proteins required by the organism, because the genes store the instructions for building those proteins. However, if the shape of the chromatin changes with age, other processes may be triggered instead, which can harm the organism.
“Chromatin acts like a filter for potential gene expression,” explains lead researcher G. V. Shivashankar from the PSI Center for Life Sciences. “Processes such as wound healing or tissue repair in the brain are impaired if the activation of the appropriate genes no longer works properly.”
Young cells versus old
Shivashankar’s team, which also includes the PhD student Yawen Liao, the first author of the study, used connective tissue cells known as fibroblasts for their research. “We could just as easily have used brain or muscle cells,” Shivashankar points out. “The mechanisms are basically comparable in all cells.” The researchers embedded the cells in a three-dimensional matrix of collagen gel, as is common practice when working with tissue samples. They then subjected this gel to mechanical tension. Normally the gel would contract like a drop of water, but a surrounding ring of glass kept it taut across its surface. They also added the growth factor TGF-β, which regulates the maturation, division and immune response of cells, as a chemical messenger. This was intended to show how the cells reacted to a biochemical signal.
“The response to the signal that we observed in the older cells was different and significantly weaker, even though the signal was exactly the same in both cases,” Yawen Liao reports. Young cells contracted against the tensile force exerted by the ring and increased their division rate. Older cells did the same, but their response was much weaker. When the ring was removed, the older cells maintained their contraction while the young cells adapted and relaxed again.
The researchers then looked into the changes in the old cells that might explain such pronounced differences in behaviour compared with the young cells. They used special imaging techniques and molecular biological methods to determine the three-dimensional structure of the chromatin at the molecular level. “Here we saw the decisive difference,” says Liao. “It seems as though chromatin opens up with age, so to speak.” Areas of the genome that were previously tightly packed and therefore inaccessible, because they contain genes that are irrelevant for that particular cell type, now become more easily accessible. “The result is an increase in incorrect activations. Instead of reading the appropriate genes for the process in question, there is an increase in the expression of unsuitable genes and the production of unwanted proteins, for example,” Liao continues. “If this gets out of hand, it can lead to diseases, including cancer.”
Can ageing cells be brought back into shape?
Shivashankar’s team wants to carry out additional experiments to investigate whether and how these findings can be used for new therapeutic approaches. “Perhaps we can selectively modify the shape of the chromatin and prevent it from changing in this way,” says Shivashankar. “Or else it might be possible to return it to a youth-like state.” Although this would certainly not stop ageing itself, it might be possible to slow down or delay age-related degeneration in specific types of tissue.
In another project, Shivashankar and other researchers have developed a new imaging technique that uses artificial intelligence to identify pathologically modified chromatin structures in high-resolution images. The AI system compares the chromatin of blood cells – which play a key role in the body’s immune response to various diseases – with the chromatin of healthy blood cells based on hundreds of characteristics such as shape, texture and light spectrum. These patterns are currently being recorded in a comprehensive reference database. In combination with this type of early detection, selectively modifying the structure of the chromatin could open up new possibilities for healthier ageing in the long term.
Text: Jan Berndorff
------------------------------------------------------------
About PSI
The Paul Scherrer Institute PSI develops, builds and operates large, complex research facilities and makes them available to the national and international research community. The institute's own key research priorities are in the fields of future technologies, energy and climate, health innovation and fundamentals of nature. PSI is committed to the training of future generations. Therefore about one quarter of our staff are post-docs, post-graduates or apprentices. Altogether PSI employs 2300 people, thus being the largest research institute in Switzerland. The annual budget amounts to approximately CHF 450 million. PSI is part of the ETH Domain, with the other members being the two Swiss Federal Institutes of Technology, ETH Zurich and EPFL Lausanne, as well as Eawag (Swiss Federal Institute of Aquatic Science and Technology), Empa (Swiss Federal Laboratories for Materials Science and Technology) and WSL (Swiss Federal Institute for Forest, Snow and Landscape Research).
Prof. Dr. G. V. Shivashankar
PSI Center for Life Sciences
Paul Scherrer Institute PSI
+41 56 310 42 50
gv.shivashankar@psi.ch
[English]
Yawen Liao
PSI Center for Life Sciences
Paul Scherrer Institute PSI
+41 56 310 55 14
yawen.liao@psi.ch
[English]
Chromatin Accessibility Regulates Age-Dependent Nuclear Mechanotransduction
Yawen Liao, Luezhen Yuan, Trinadha Rao Sornapudi, Max Land, Rajshikhar Gupta, G. V. Shivashankar
PNAS, 27.03.2026
DOI: 10.1073/pnas.2522217123
G. V. Shivashankar (left) and Yawen Liao from the PSI Center for Life Sciences have investigated how ...
Source: Markus Fischer
Copyright: Paul Scherrer Institute PSI
“It seems as though chromatin opens up with age, so to speak,” says PSI scientist Yawen Liao. “The r ...
Source: Markus Fischer
Copyright: Paul Scherrer Institute PSI
Criteria of this press release:
Journalists
Biology, Medicine
transregional, national
Research results
English
You can combine search terms with and, or and/or not, e.g. Philo not logy.
You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).
Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.
You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).
If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).
