Theoretical framework uncovers coupled physical and biochemical degradation loops in aging skin, suggesting multitargeted tissue-level anti-aging interventions.
Key Points
To propose and substantiate an integrative, tissue-level framework that links physical microenvironmental decay with biochemical dysfunction during early skin aging.
Synthesized literature on dermal fluid dynamics, extracellular matrix biomechanics, cellular mechanotransduction, and metabolic signaling pathways.
Modeled the cross-talk between physical microenvironmental cues and intracellular nutrient-sensing networks to establish a coupled feedback framework.
Identified three coupled drivers of skin aging: dermal fluid dynamics decay (reduced interstitial fluid pressure and flow), mechanical unloading of fibroblasts via matrix fragmentation, and nutrient-sensing pathway dysregulation (mTOR, AMPK, SIRT1).
Demonstrated that mechanosensitive pathways, specifically the integrin-YAP/TAZ signaling axis, serve as the primary bridge translating physical matrix unloading into biochemical decline.
Characterized a self-reinforcing positive feedback loop that drives progressive tissue-level structural and functional deterioration.