Mechanical rejuvenation of senescent stem cells and aged bone via chromatin remodeling.

ABSTRACT: Bone aging compromises skeletal integrity and increases vulnerability to osteoporosis and other age-related disorders, underscoring the need for new therapeutic strategies. Although pharmacological and genetic approaches have been widely explored, how cellular mechanical remodeling contributes to bone aging remains unclear. Here, we find that senescent bone marrow stem cells show markedly reduced intracellular force and impaired mechanical behavior. Moderate mechanical stimulation in cell culture and in mice restores cellular force, increases chromatin accessibility at the FOXO1 locus, activates its expression, and reverses cellular senescence and bone aging. These mechanical interventions also improve physical performance in aged female mice and show a tendency to reduce systemic inflamma

SUBMITTER: Liu X 

PROVIDER: S-EPMC12910031 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature