In the short-lived African killifish Nothobranchius furzeri, an intermittent fasting regimen extended lifespan in both males and females, at the cost of reduced growth and reproductive output, and improved swimming performance in old animals of both sexes. Muscle aging differed by sex: males gained myofibers (hyperplasia) while females kept fiber number but enlarged fibers. Fasting partially normalized both patterns. Single-nucleus sequencing showed fasting restored IGF signaling in females and ANGPTL signaling in males, while upregulating ribosome biogenesis and contractile-apparatus genes in both.
The evidence here comes from fish, not people, so it cannot guide fasting practice. Its value is conceptual. Killifish live only months, making them a fast model for testing interventions, but a lifespan extension in them has often failed to translate to mammals. The most interesting result is the convergence: different cellular routes to the same outcome, with a shared anabolic signature (ribosome biogenesis, myofibrillar maintenance) that echoes how exercise and protein sufficiency protect human muscle. That complicates the common assumption that fasting is catabolic for muscle. The reproductive and growth trade-offs also mirror caloric restriction literature in rodents. For human relevance, most intermittent fasting trials remain short and rarely report sex-stratified muscle outcomes, so the call to treat sex as a biological variable is well placed. Treat this as a solid, incremental mechanistic contribution, hypothesis-generating rather than practice-changing.
