Mechanical memory in aging: From adaptive sensing to pathological entrenchment

Abstract Cells can carry forward information from earlier mechanical environments and not only respond to the cue in front of them. This property, usually described as mechanical memory, is important for aging because many old tissues stiffen, whereas their resident cells become less regenerative and less mechanosensitive. This mismatch suggests that aging changes the handling of mechanical information: how it is sensed, transmitted, stored, and used. Here, we review evidence across cytoskeletal organization, focal adhesions and ion channels, nuclear mechanics, chromatin, biomolecular condensates, and metabolism. We treat epigenetic memory as one durable execution layer within mechanical memory and not as a synonym for the whole process. We then use three failure modes—sensor degradation, conduction blockade, and execution blockade—to organize aging‐related mechanical‐memory failure. This scheme helps explain why similar modules, including YAP/TAZ, the LINC complex, and repressive chromatin marks, have different consequences in skeletal muscle, bone and cartilage, lung, heart, skin, and brain. We also discuss condensate maturation and liquid‐to‐solid transitions as possible consolidation mechanisms, while emphasizing that direct in vivo evidence of normal aging remains limited. Finally, we classify therapeutic ideas by target layer, evidence strength, reversibility, and translational risk. The review therefore frames mechanical memory as a multilayer, tissue‐dependent process that may help explain why physical history contributes to degeneration with age.