Mechanical signals in aging: mechanisms and therapeutic strategies

Cellular senescence is a fundamental driver of aging and age-related diseases. While traditionally attributed to biochemical cues, accumulating evidence identifies cellular mechanics as a critical regulator of senescence. Cells continuously sense and transduce extracellular mechanical signals, which reshape cytoskeletal architecture, nuclear mechanics, and chromatin organization. In this review, we summarize multi-scale mechanical alterations associated with senescence, including altered cellular traction force, cytoskeletal disorganization, and impaired nuclear mechanotransduction. We further discuss key mechanosensitive pathways that govern senescence initiation and progression. Finally, we highlight emerging mechanical approaches for identifying senescent cells and discuss the therapeutic potential of mechanics-based interventions, including mechanical stimulation, microenvironment remodeling, and targeted modulation of mechanotransduction, for aging and regenerative medicine.