Tocchetti A , Ekalle Soppo CB , Zani F , Bianchi F , Gagliani MC , Pozzi B , Rozman J , Elvert R , Ehrhardt N , Rathkolb B , Moerth C , Horsch M , Fuchs H , Gailus-Durner V , Beckers J , Klingenspor M , Wolf E , de Angelis MH , Scanziani E , Tacchetti C ,
PLoS One.2010 ; 5(3):e9468.
PMID: 20209148[PubMed - as supplied by publisher]
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.