Why do cells respond “incorrectly” in old age?

What is it about?

As we age, our cells start responding incorrectly to signals from their environment. We have shown that the packed form of DNA in the cell nucleus, known as chromatin, changes with aging, making older cells far less flexible. When we exposed young and old skin cells to the same mechanical forces and biochemical signals, young cells integrated both signals and responded vigorously, while old cells showed a much weaker, sometimes completely wrong response. The reason is that chromatin acts like a filter for gene activity: when its structure changes with age, genes are read differently, or not at all. This can disrupt repair processes and contribute to age-related diseases.

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Photo by Rod Long on Unsplash

Photo by Rod Long on Unsplash

Why is it important?

We show for the first time that the 3D organization of chromatin, how DNA is folded inside the nucleus, acts as a filter that determines how cells integrate simultaneous mechanical and biochemical signals, and that aging specifically degrades this filter. This reframes how we understand age-related cellular dysfunction: it is not simply that individual signaling proteins wear out, but that the genome's physical architecture loses its ability to coordinate responses. Our identification of AP-1 as a central regulator of this process provides a concrete molecular target for future therapies aimed at healthy aging.

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