Summary
Researchers at the Paul Scherrer Institute PSI have demonstrated that the packed form of DNA (chromatin) in the cell nucleus changes with age. This causes older cells to respond more weakly and incorrectly to external signals. The study, published in the journal PNAS, analyzed skin cells from ten-year-old children and 75-year-old people under mechanical stress and growth factors. The findings could enable new therapeutic approaches to slow age-related degeneration.
People
- G.V. Shivashankar (Study Leader, PSI Center for Life Sciences)
- Yawen Liao (First Author, PhD Student)
Topics
- Cell aging and chromatin structure
- Gene expression and cell reactions
- Age-related diseases
- Regenerative medicine and therapeutic approaches
Clarus Lead
The research addresses a fundamental problem in gerontology: why cells not only age but increasingly respond incorrectly to biological signals. With the identification of chromatin changes as a primary mechanism, a concrete point of intervention emerges – not to prevent aging itself, but to deliberately slow age-associated degeneration in individual tissues. The parallel development of an AI-assisted imaging technique for early detection of pathological chromatin structures signals the transition from basic research to clinical applicability.
Detailed Summary
The research team led by Shivashankar investigated the mechanical responsiveness of fibroblasts (connective tissue cells) from different age groups. The cells were embedded in a three-dimensional collagen matrix and exposed to mechanical stress, while the growth factor TGF-β was simultaneously added as a biochemical signal. Young cells contracted against the external tensile force and increased their division rate; after removal of the stress, they adapted and relaxed. Older cells showed a significantly weakened response and maintained their contraction – a sign of impaired adaptability.
Molecular biological analysis of the three-dimensional chromatin structure revealed the mechanism: with age, chromatin opens up, so to speak. Previously condensed genomic regions containing irrelevant genes for the respective cell type become accessible. This leads to misactivations, in which inappropriate genes are transcribed and unwanted proteins are produced. Liao emphasizes that this dysregulation, when excessive, can lead to diseases including cancer. Chromatin thus functions as a critical filter for precise gene expression – a function that becomes impaired with age.
Shivashankar plans further studies on the therapeutic use of these findings: targeted modification of chromatin structure could prevent or reverse age-related changes. In parallel, the team developed an AI-assisted imaging technique that identifies pathological chromatin structures in blood cells using hundreds of features (shape, texture, light spectrum). A comprehensive reference database of healthy blood cells is currently being built. This combination of early detection and targeted chromatin modification could eventually open new paths for healthier aging.
Key Findings
- Chromatin structure changes with age and becomes more accessible to irrelevant genes
- Faulty gene expression leads to misactivations and can trigger diseases
- Older cells show reduced and incorrectly adapted responses to external signals
- Therapeutic interventions to modulate chromatin structure are under development
- AI-assisted imaging enables early detection of pathological chromatin structures
Critical Questions
Evidence/Source Validity: How representative are skin cell samples (fibroblasts) for age-related chromatin changes in other tissues such as nerve or muscle cells, and have these already been investigated?
Data Quality: What sample size was used in the analysis of cells from ten-year-old versus 75-year-old individuals, and how was control for interindividual genetic variation performed?
Causality: Is the observed chromatin opening a cause or consequence of age-related cellular dysfunction, or does a bidirectional mechanism exist?
Alternatives: Could other factors such as mitochondrial dysfunction or telomere shortening explain the observed response differences, and were these excluded?
Feasibility: What specific molecular targets for chromatin modulation have been identified, and at what development stage are corresponding active compounds?
Side Effects: Could artificial modification of chromatin structure trigger undesirable effects such as increased cancer risk through uncontrolled gene activation?
Conflicts of Interest: What funding supports the development of the AI imaging technique, and are commercial exploitation interests present?
References
Primary Source: 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
Verification Status: ✓ 27.03.2026
This text was created with the support of an AI model. Editorial Responsibility: clarus.news | Fact-Check: 27.03.2026