Fondazione Instituto FIRC di Oncologia Molecolare, Milan, Italy.
PLoS One. 2010 Mar 2;5(3):e9468. doi: 10.1371/journal.pone.0009468.
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.
在包括哺乳动物在内的多种生物体中，热量限制可改善代谢状况并降低慢性退行性疾病的发病率，从而最终延长寿命。
方法/主要发现：在这里，我们表明 Eps8（一种肌动蛋白动力学调节剂）的敲除小鼠体重减轻，对年龄或饮食引起的肥胖具有部分抗性，并且整体代谢状况得到改善。肝脏基因表达谱、行为和代谢的改变表明 Eps8 敲除小鼠具有类似于热量限制的表型。此外，与热量限制代谢一致，Eps8 敲除小鼠的寿命延长。Eps8 敲除小鼠的代谢变化与肠道脂肪吸收的显著减少相关，这可能是由于肠微绒毛长度减少了 25%。
结论/意义：我们的发现表明肌动蛋白动力学是决定寿命的一个新的变量。此外，我们的观察结果表明，能量平衡的细微差异随着时间的推移会显著影响小鼠的体重和代谢状态。
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