Peter J Houweling

Submitted: 17 December 2025 You are already at the latest version Muscle regeneration following injury reveals a striking paradox: the same phenomenon, fiber branching, can serve as both a beneficial adaptation in healthy muscle and a pathological hallmark in disease. In healthy muscle, branched fibers emerge as an adaptive response to extreme mechanical loading, redistributing stress, enhancing hypertrophy, and protecting against injury.

Abstract A nonsense polymorphism in the ACTN3 gene (R577X, rs1815739) results in the loss of the fast skeletal muscle fiber protein α-actinin-3 in an estimated 1.5 billion humans worldwide. Homozygosity for this common polymorphism (ACTN3 577XX) does not cause disease but is detrimental to sprint performance in elite athletes. Recently, we reported that ACTN3 577XX humans and Actn3 knockout mice show improved cold tolerance.