The DECIPHER system. Credit: Nature Materials (2025). DOI: 10.1038/s41563-025-02234-6

A new lab-grown material has revealed that some of the effects of aging in the heart may be slowed and even reversed. The discovery could open the door to therapies that rejuvenate the heart by changing its cellular environment, rather than focusing on the heart cells themselves.

The research, published in Nature Materials, was carried out by a team led by Assistant Professor Jennifer Young from the Department of Biomedical Engineering in the College of Design and Engineering (CDE) at the National University of Singapore (NUS). Asst Prof Young is also a scientist at the NUS Mechanobiology Institute (MBI).

The team focused on the extracellular matrix (ECM)—the complex framework that surrounds and supports heart cells. This net-like scaffolding made of proteins and other components holds cells in place and sends chemical signals that guide how the cells function.

As the heart ages, the ECM becomes stiffer and its biochemical composition changes. These changes can trigger harmful activity in heart cells, contributing to scarring, loss of flexibility, and reduced function.

"Most aging research focuses on how cells change over time, " said Asst Prof Young. "Our study looks instead at the ECM and how changes in this environment affect heart aging."

To investigate this, the team developed a hybrid biomaterial called DECIPHER (DECellularized In Situ Polyacrylamide Hydrogel-ECM hybrid), made by combining natural heart tissue with a synthetic gel to closely mimic the stiffness and composition of the ECM.

Asst Prof Jennifer Young (right) and PhD student Avery Rui Sun (left), who are from the College of Design and Engineering at NUS, image heart cells (orange) on DECIPHER scaffolds (pink) using a confocal microscope to understand how cells interact with the extracellular matrix. Credit: National University of Singapore

"Until now, it's been difficult to pinpoint which of these changes—physical stiffness or biochemical signals—play the bigger role in driving this decline, because they usually happen at the same time, " said Avery Rui Sun, Ph.D. student at NUS CDE and MBI, and first author of the study.

"The DECIPHER platform solves this problem, allowing researchers to independently control the stiffness and the biochemical signals presented to the cells—something no previous system using native tissue has been able to do."

When the team placed aged heart cells onto DECIPHER scaffolds that mimicked "young" ECM cues, they found that the cells began to behave more like young cells—even when the material remained stiff. Closer investigation revealed that this included a shift in gene activity across thousands of genes associated with aging and cell function.

In contrast, young cells placed on "aged" ECM began to show signs of dysfunction, even if the scaffold was soft.

"This showed us that the biochemical environment around aged heart cells matters more than stiffness, while young cells take in both cues, " said Asst Prof Young.

The DECIPHER sample consists of heart tissue (centre) embedded within a stiffness-tuneable hydrogel. Credit: National University of Singapore

"Even when the tissue was very stiff, as it typically is in aged hearts, the presence of 'young' biochemical signals was enough to push aged cells back toward a healthier, more functional state, " she added. "This suggests that if we can find a way to restore these signals in the aging heart, we might be able to reverse some of the damage and improve how the heart functions over time."

"On the other hand, for young heart cells, we found that higher stiffness can cause them to prematurely 'age', suggesting that if we target specific aspects of ECM aging, we might slow or prevent heart dysfunction over time."

While the work is still in the research phase, the team says their findings open up a new direction for therapies aimed at preserving or restoring heart health during aging—by targeting the ECM itself.

They hope the method could also be adapted to study other tissues affected by aging and disease. Beyond the heart, the team believes the DECIPHER method could be applied to study aging and disease in other organs as well, due to the major role of the ECM in cell function across all our tissues.

"Many age-related diseases involve changes in tissue stiffness—not just in the heart, " said Asst Prof Young. "For example, the same approach could be applied to kidney and skin tissue, and it could be adapted to study conditions like fibrosis or even cancer, where the mechanical environment plays a major role in how cells behave."

More information: Avery Rui Sun et al, Hybrid hydrogel–extracellular matrix scaffolds identify biochemical and mechanical signatures of cardiac ageing, Nature Materials (2025). DOI: 10.1038/s41563-025-02234-6  Journal information: Nature Materials