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Tocchetti A.,Fondazione Instituto Firc Of Oncologia Molecolare | Tocchetti A.,KtedoGen Srl | Soppo C.B.E.,Fondazione Instituto Firc Of Oncologia Molecolare | Zani F.,Fondazione Instituto Firc Of Oncologia Molecolare | And 34 more authors.
PLoS ONE | Year: 2010

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. © 2010 Tocchetti et al.

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