Extracellular matrix (ECM) aging

The extracellular matrix (ECM) is the protein and proteoglycan scaffold that provides structural support and transmits biochemical and mechanical signals to resident cells; with age, it undergoes progressive stiffening, fragmentation, and compositional remodelling driven by accumulated crosslinks, glycation end-products, reduced matrix turnover, and dysregulated matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) balance. ECM stiffening alters integrin-mediated mechanosignalling, promotes pro-fibrotic TGF-beta pathways, and has been shown to reinforce the SASP of senescent cells in a feed-forward loop. These changes impair tissue repair, compromise stem cell niches, and contribute to pathologies including cardiac fibrosis, osteoarthritis, and age-related pulmonary decline, making ECM integrity an emerging target for longevity-focused interventions.