Nature communicationsJan 12, 2026

Using Mechanical Forces to Restore Aging Stem Cells and Bones by Changing Their DNA Structure

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Moderate mechanical stimulation may counter age-related bone decline by restoring force-related FOXO1 signaling in senescent stem cells.

Evidence

A cell and mouse preclinical study tested mechanical stimulation in senescent bone marrow stem cells and aged female mice, linking moderate force to FOXO1 activation, reduced senescence and bone aging, and improved physical performance.

Caveat

The work is preclinical, systemic inflammation only showed a tendency to decrease, and excessive force caused chromatin overextension and DNA damage.

Simplified

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 inflammation, whereas excessive force induces chromatin overextension and DNA damage, indicating the necessity of precise force control. In this work, we show that optimized mechanical stimulation provides a simple and effective strategy to counteract age-related bone deterioration and systemic inflammation, offering potential for clinical translation.