Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, Quebec City, Canada.
Ann N Y Acad Sci. 2010 Jun;1197:40-4. doi: 10.1111/j.1749-6632.2010.05189.x.
Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many phenotypic features of WS. Importantly, mutant Wrn(Deltahel/Deltahel) mice show abnormal increases in visceral fat deposition and fasting blood triglyceride levels followed by insulin resistance and high blood glucose levels. These mice also exhibit increased heart and liver tissue reactive oxygen species concomitantly with oxidative DNA damage, indicating a pro-oxidant status. We treated mice with either ascorbate or catechin hydrate for 9 months. Vitamin C supplementation reduced oxidative stress in liver and heart tissues and reversed hypertriglyceridemia, hyperglycemia, and insulin resistance and reduced fat weight in mutant Wrn(Deltahel/Deltahel) mice. Although the free scavenger catechin hydrate also reduced oxidative DNA damage in heart and liver tissues, it did not reverse any of the metabolic phenotype aspects in treated mutant mice. Finally, vitamin C and catechin hydrate did not affect the metabolic status of wild-type mice. These results indicate that vitamin C supplementation could be beneficial for WS patients.
沃纳综合征（WS）是一种由 RecQ 样 DNA 解旋酶突变引起的过早衰老疾病。缺乏 WRN 同源物解旋酶结构域的小鼠表现出许多 WS 的表型特征。重要的是，突变型 Wrn(Deltahel/Deltahel)小鼠表现出内脏脂肪沉积和空腹血甘油三酯水平异常增加，随后出现胰岛素抵抗和高血糖水平。这些小鼠还表现出心脏和肝脏组织活性氧的增加伴随着氧化 DNA 损伤，表明存在促氧化剂状态。我们用抗坏血酸或儿茶素水合物治疗小鼠 9 个月。维生素 C 补充剂降低了肝脏和心脏组织的氧化应激，逆转了突变型 Wrn(Deltahel/Deltahel)小鼠的高甘油三酯血症、高血糖和胰岛素抵抗，并减少了脂肪重量。尽管游离清除剂儿茶素水合物也降低了心脏和肝脏组织的氧化 DNA 损伤，但它并没有逆转治疗后的突变型小鼠的任何代谢表型方面。最后，维生素 C 和儿茶素水合物对野生型小鼠的代谢状态没有影响。这些结果表明，维生素 C 补充可能对 WS 患者有益。
