In the short-lived killifish Nothobranchius furzeri, intermittent fasting extended lifespan and preserved swimming performance in both sexes, but the underlying muscle remodeling diverged sharply by sex. Males showed age-related myofiber hyperplasia while females shifted toward oxidative slow-twitch fibers, and fasting corrected each pattern through different signaling routes — IGF in females, ANGPTL in males. The shared benefit was increased ribosome biogenesis and expression of contractile and myofibrillar genes, pointing to a conserved anabolic mechanism behind fasting-related muscle preservation.
Key Points
- Intermittent fasting extended lifespan and preserved swimming capacity in both sexes
- Muscle aging diverged by sex: male hyperplasia, female hypertrophic remodeling
- Fasting restored IGF signaling in females, ANGPTL signaling in males
Longevity Analysis
Fasting protocols are frequently prescribed as sex-neutral, yet the cellular route to preserved muscle differs enough that identical regimens may produce unequal outcomes in strength, fiber composition, and metabolic signaling. The lifespan gain came with measurable trade-offs — reduced growth and reproductive output — which reframes caloric timing as an allocation decision rather than a cost-free addition. Functional capacity, not fiber count, tracked most closely with benefit, making movement performance a more honest readout of muscle aging than mass alone, and arguing for monitoring that distinguishes structural change from signaling decline across the tissue.
Original published by Wiley Aging Cell, by Sonia Sandhi, Hannah Somers, Matthew Cox, Celeste Nobrega, Ryan Seaman, Elizabeth Baker, Olivia Lentchner, Robyn Reeve, Romain Menard, James Godwin, Anastasia Paulmann, Aric Rogers, Dario Riccardo Valenzano, Joel H. Graber, Hermann Haller, Romain Madelaine .