Biomaterial helps to reverse aging in the heart

Using a lab-grown material, researchers at the National University of Singapore (NUS) have revealed that some of the effects of aging in the heart may be slowed and even reversed. Their discovery, which has been published in the journal Nature Materials, could open the door to therapies that rejuvenate the heart by changing its cellular environment, rather than the heart cells themselves.

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 team leader Assistant Professor Jennifer Young. “Our study looks instead at the ECM and how changes in this environment affect heart aging.”

According to PhD student Avery Rui Sun, it has until now been difficult to pinpoint whether physical stiffness or biochemical signals play the bigger role in driving heart aging, because they usually happen at the same time. 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.

“The DECIPHER platform … [allows] 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,” Sun said.

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,” Young said.

“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. 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 researchers said their findings open up a new direction for therapies aimed at preserving or restoring heart health during aging — by targeting the ECM itself. Beyond the heart, they believe the DECIPHER method could be applied to studying 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,” Young said. “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.”

Image caption: The DECIPHER sample consists of heart tissue (centre) embedded within a stiffness-tuneable hydrogel.