This review examines how ECM remodeling (collagen crosslinking, elastin loss, basement membrane thickening), vascular dysfunction, and mitochondrial impairment interact in a self-reinforcing loop to drive tissue aging and functional decline.
The authors propose a feedback loop: ECM stiffening → reduced vascular compliance and angiogenesis → hypoperfusion/hypoxia → inhibited oxidative phosphorylation and excess ROS → ATP deficit → cellular senescence and inflammation → further ECM stiffening, accelerating tissue aging.
This is a narrative/mechanistic review with no original clinical or experimental data; proposed mechanisms and therapeutic targets are speculative and not yet validated in human trials.
Clinicians should be aware that ECM stiffness, vascular integrity, and mitochondrial health may represent linked, co-targetable axes in aging-related tissue decline. Therapeutic strategies addressing any one node (e.g., anti-fibrotic agents, mitochondrial support) may have broader downstream effects on the aging trajectory.
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