Physiomimetic 3D skeletal muscle reveals senescence-driven matreotype remodeling driving paracrine senescence and regenerative failure

Senescence was induced in 3D constructs by a single 20 Gy X-ray irradiation, resulting in impaired myogenic differentiation and structural maturation. To define senescence-associated transcriptional programs and paracrine senescence, we performed bulk RNA-sequencing on (i) irradiated senescent (SnC) versus (ii) non-irradiated normal 3D muscle constructs, and (iii) normal constructs exposed in a co-culture to senescent construct–derived secretome (SASP).

These datasets enable quantitative characterization of senescence-driven gene expression changes linked to ECM remodeling, inflammation, and loss of myogenic/contractile programs in a physiologically relevant 3D muscle model.