Altered cell crosstalk marks muscle disuse recovery in older women

In a preprint, researchers analyzed skeletal muscle and primary cells from eight young women (aged 22±3 years) and nine older women (aged 66±5 years) during recovery from disuse atrophy. At seven days of recovery, transcriptional changes were markedly broader in older women across slow- and fast-twitch myonuclei, satellite cells, and fibro-adipogenic progenitors (FAPs). Satellite cells from older women showed collagen signatures, including elevated THBS1 expression and enriched TGF-beta signaling, while FAPs exhibited higher expression of the activation marker ADAMTS14. Analyses also identified altered communication between FAPs and satellite cells. In complementary cell culture experiments, myogenic progenitor cells isolated from older women at seven days of recovery displayed impaired differentiation and a senescence-associated phenotype. Exposing cells to conditioned media from older donors' fibroblasts further increased senescence markers and impaired myogenic potential compared with media from younger donors.