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首页> 美国卫生研究院文献>other >Health Effects of Long-Term Rapamycin Treatment: The Impact on Mouse Health of Enteric Rapamycin Treatment from Four Months of Age throughout Life
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Health Effects of Long-Term Rapamycin Treatment: The Impact on Mouse Health of Enteric Rapamycin Treatment from Four Months of Age throughout Life

机译：雷帕霉素长期治疗的健康影响：整个生命周期四个月大时对雷帕霉素肠溶治疗对小鼠健康的影响

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Rapamycin, an mTOR inhibitor, has been shown to extend lifespan in a range of model organisms. It has been reported to extend lifespan in multiple strains of mice, administered chronically or acutely early or late in life. The ability of rapamycin to extend health (healthspan) as opposed to life is less well documented. To assess the effects chronic rapamycin treatment on healthspan, enteric rapamycin was given to male and female C57BL/6J mice starting at 4 months of age and continued throughout life. Repeated, longitudinal assessments of health in individual animals were made starting at 16 months of age (=12 months of treatment) until death. A number of health parameters were improved (female grip strength, female body mass and reduced sleep fragmentation in both sexes), others showed no significant difference, while at least one (male rotarod performance) was negatively affected. Rapamycin treatment affected many measures of health in a highly sex-specific manner. While sex-specific phenotypic effects of rapamycin treatment have been widely reported, in this study we document sex differences in the direction of phenotypic change. Rapamycin-fed males and females were both significantly different from controls; however the differences were in the opposite direction in measures of body mass, percent fat and resting metabolic rate, a pattern not previously reported.
机译：雷帕霉素是一种mTOR抑制剂，已被证明可以延长多种模型生物的寿命。据报导，在生命早期或晚期长期或急性施用多种小鼠品系可以延长寿命。雷帕霉素延长健康（延长寿命）而不是延长生命的能力的文献较少。为了评估慢性雷帕霉素治疗对健康期的影响，从4个月大时开始对雄性和雌性C57BL / 6J小鼠进行肠溶雷帕霉素治疗，并持续终生。从16个月大（=治疗12个月）开始直至死亡，均对动物进行了重复的纵向健康评估。改善了许多健康参数（女性的抓地力，女性体重和减少的睡眠破碎率），其他参数没有显着差异，而至少一个参数（男性轮转机性能）受到了负面影响。雷帕霉素的治疗以高度性别特异性的方式影响了许多健康指标。尽管已经广泛报道了雷帕霉素治疗的性别特异性表型效应，但在这项研究中，我们记录了表型改变方向上的性别差异。雷帕霉素喂养的雄性和雌性均与对照组有显着差异。但是，在体重，脂肪百分比和静息代谢率的测量方法上却是相反的方向，以前没有报道过这种模式。

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