Does collagen gel stiffness crossing ~8 kPa trigger a discontinuous epigenetic clock entropy jump in aged fibroblasts?
Why this is novel: First systematic ECM stiffness titration against whole-genome epigenetic clock. The Kramers bistability framing — imported from condensed matter physics — predicts a discontinuous phase transition in epigenetic age at a specific mechanical threshold. This connection has never been tested.
If ECM stiffness gates epigenetic age via a bistable switch, mechanical rejuvenation of the matrix is as therapeutically relevant as chemical senolytics or OSK reprogramming — a completely new intervention axis. A positive result immediately motivates ECM-softening biologics (MMP activators, LOXL2 inhibitors) as anti-aging drugs.