Some of the changes we associate with ageing begin deep inside our cells, particularly in the nucleus where DNA is stored. DNA is not loose; it is tightly packaged into a structure called chromatin. Researchers at the Paul Scherrer Institute (PSI) have shown that this packaging changes as we grow older. These changes affect how cells read genetic instructions and respond to signals from their environment. As a result, older cells may react less effectively—or even incorrectly—which can contribute to disease. The findings were published in the journal Proceedings of the National Academy of Sciences.
As people age, their cells do not simply stop working, but they do become less flexible. They divide less often and may not respond properly to external signals. The PSI researchers found that the root of this problem lies in chromatin. When chromatin changes shape, it affects how genes are turned on or off. Genes contain the instructions for making proteins, which cells need to function properly. If these instructions are not read correctly, the cell may produce the wrong proteins or fail to respond when needed.
To study this, the scientists examined skin cells from both young and older individuals. They compared cells from children around ten years old with those from adults aged 75. Using microscopes and molecular techniques, they exposed the cells to mechanical stress and a chemical signal known as TGF-β, which normally helps regulate cell growth and repair. Younger cells responded strongly—they contracted and increased their activity. Older cells also reacted, but their response was noticeably weaker and less adaptable.
The researchers then looked more closely at what was happening inside the cells. They found that chromatin in older cells becomes more “open.” This means that parts of the DNA that should remain tightly packed and inactive become easier to access. While this might sound helpful, it actually leads to problems. The cell begins to activate genes that are not needed, while failing to activate the ones that are needed properly. This mix-up can result in the production of unnecessary or harmful proteins and may increase the risk of diseases, including cancer.
According to lead researcher G. V. Shivashankar, chromatin acts like a filter that controls which genes are used at any given time. When this filtering system breaks down, important processes such as wound healing or tissue repair may not work properly. This helps explain why the body becomes less efficient at recovering from injury or illness with age.
Looking ahead, the research team hopes to find ways to control or even reverse these changes in chromatin. If scientists can restore chromatin to a more “youthful” state, it may be possible to improve how cells function in older adults. While this would not stop ageing entirely, it could help delay some of its negative effects. The team is also developing new tools, including artificial intelligence, to detect harmful changes in chromatin early. Together, these advances could open the door to healthier ageing in the future.
More information: Yawen Liao et al, Chromatin accessibility regulates age-dependent nuclear mechanotransduction, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2522217123
Journal information: Proceedings of the National Academy of Sciences Provided by Paul Scherrer Institute
