Tocchetti, Arianna Soppo, Charlotte Blanche Ekalle Zani, Fabio Bianchi, Fabrizio Gagliani, Maria Cristina Pozzi, Benedetta Rozman, Jan Elvert, Ralf Ehrhardt, Nicole Rathkolb, Birgit Moerth, Corinna Horsch, Marion Fuchs, Helmut Gailus-Durner, Valérie Beckers, Johannes Klingenspor, Martin Wolf, Eckhard Hrabé de Angelis, Martin Scanziani, Eugenio Tacchetti, Carlo Scita, Giorgio Di Fiore, Pier Paolo Offenhäuser, Nina 2010-03-02 Background: In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Methodology/Principal Findings: Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length. Conclusions/Significance: Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice. application/pdf https://folia.unifr.ch/unifr/documents/301609 https://folia.unifr.ch/documents/301609/files/zan_lar.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0009468 info:eu-repo/semantics/openAccess License undefined PLoS ONE. - 2010, vol. 5, no. 3, p. e9468 info:eu-repo/classification/udc/57 Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice http://purl.org/coar/resource_type/c_6501