Reduction of senescent fibro‐adipogenic progenitors in progeria‐aged muscle by senolytics rescues the function of muscle stem cells

Abstract Background Fibro‐adipogenic progenitors (FAPs) in the muscles have been found to interact closely with muscle progenitor/stem cells (MPCs) and facilitate muscle regeneration at normal conditions. However, it is not clear how FAPs may interact with MPCs in aged muscles. Senolytics have been demonstrated to selectively eliminate senescent cells and generate therapeutic benefits on ageing and multiple age‐related disease models. Methods By studying the muscles and primary cells of age matched WT mice and Zmpste24−/− (Z24−/−) mice, an accelerated ageing model for Hutchinson–Gilford progeria syndrome (HGPS), we examined the interaction between FAPs and MPCs in progeria‐aged muscle, and the potential effect of senolytic drug fisetin in removing senescent FAPs and improving the function of MPCs. Results We observed that, compared with muscles of WT mice, muscles of Z24−/− mice contained a significantly increased number of FAPs (2.4‐fold; n > =6, P =6, P =6, P =6, P =6, P =6, P =6, P =6, P =6, P