Scientists rewind heart ageing using lab-grown scaffold that mimics young tissue

Over time, this scaffolding stiffens and its chemical cues go haywire, setting off a domino effect that leads to scarring, loss of flexibility, and fading heart function.

Matrix, not muscle, matters

To explore this overlooked angle, the researchers built a hybrid biomaterial called DECIPHER (DECellularized In Situ Polyacrylamide Hydrogel-ECM hybrid).

By fusing natural heart tissue with a synthetic gel, they created a platform that closely mimics the ECM’s stiffness and biochemical makeup, allowing scientists to tweak it independently.

 “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, the 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 cultured aged heart cells on DECIPHER scaffolds designed to replicate the biochemical signals of youthful tissue, the cells began to exhibit characteristics typically seen in younger cells.

Notably, this rejuvenation occurred even when the underlying material remained stiff.

Further analysis revealed widespread changes in gene expression, involving thousands of genes associated with ageing and cellular function.

Young again by design

Conversely, when young heart cells were placed on scaffolds mimicking the aged extracellular matrix, they began to show early signs of dysfunction, even in the absence of increased stiffness, highlighting the critical influence of biochemical cues in the cellular environment.

According to Young, the findings suggest that for aged cells, the surrounding biochemical environment plays a more dominant role than stiffness in driving dysfunction.

“This suggests that if we can find a way to restore these signals in the ageing 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 ageing, we might slow or prevent heart dysfunction over time.”

While the work remains in the research phase, the team believes their findings open up a promising new avenue for therapies aimed at preserving or restoring heart function during ageing by targeting the ECM itself.

They are hopeful that the DECIPHER platform could be adapted to investigate ageing and disease in other tissues as well, given the ECM’s fundamental role in regulating cell behavior across the body.

“Many age-related diseases involve changes in tissue stiffness—not just in the heart,” said 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.”

The research has been published recently in the journal Nature Materials.