Ramli Md Faris H, Aguado Brian A, Young Jennifer L
Mechanobiology Institute (MBI), National University of Singapore, 117411, Singapore.
Shu Chien-Gene Lay Department of Bioengineering, University of California, La Jolla, San Diego, CA, 92093, USA; Sanford Consortium for Regenerative Medicine, La Jolla, CA, 92037, USA; Program in Materials Science and Engineering, University of California, La Jolla, San Diego, CA, 92093, USA.
Curr Opin Cell Biol. 2025 May 9;95:102524. doi: 10.1016/j.ceb.2025.102524.
During aging, the cardiac extracellular matrix (ECM) undergoes gradual remodeling that reduces the heart's ability to function. Specific ECM changes cause alterations in cellular signaling pathways, eliciting maladaptive responses. Here, we provide insight into the current knowledge of how age-specific ECM changes contribute to altered ligand-receptor interactions, dysregulated mechanotransduction, and the propagation of pro-fibrotic signaling cascades that underpin dysfunction. We also highlight regional and sex differences that new biomolecular and bioengineered technologies have recently uncovered. We call for new biomaterial strategies that mimic spatiotemporal and sex-specific ECM alterations to equip researchers with the tools to unravel complex cellular signaling events. We believe this can be achieved through interdisciplinary cooperation amongst researchers spanning matrix biology, biomaterials, spatial omics, and biomedical engineering.
在衰老过程中，心脏细胞外基质（ECM）会逐渐重塑，从而降低心脏的功能。特定的ECM变化会导致细胞信号通路改变，引发适应不良的反应。在此，我们深入探讨了目前关于特定年龄的ECM变化如何导致配体-受体相互作用改变、机械转导失调以及促纤维化信号级联反应的传播（这些是功能障碍的基础）的知识。我们还强调了新的生物分子和生物工程技术最近发现的区域和性别差异。我们呼吁采用新的生物材料策略，模拟时空和性别特异性的ECM变化，为研究人员提供工具来揭示复杂的细胞信号事件。我们相信，这可以通过基质生物学、生物材料、空间组学和生物医学工程等领域的研究人员之间的跨学科合作来实现。
