SENESCENT CHANGES IN METABOLISM

老年人是一个特殊的群体，他们往往面临更大的风险。 对环境因素的毒性作用敏感。 老年人体内外源性物质的处置和/或生物转化的改变 受试者可能是这种增强的易感性的一个促成因素。 在 在这个实验室里，工作的重点是随着年龄的增长而发生的变化， 环境污染物的吸收、分布、代谢和排泄 毒物，使用两种啮齿动物模型的老化。 苯是一种广泛存在的 环境污染物和人类致癌物， 以前没有在老年受试者中评估过毒性。 处置 在10和200 mg/kg剂量下，对老年小鼠苯的代谢进行了研究。 此外，使用基于生理学的药代动力学模型来获得 进一步深入了解苯的年龄相关差异的基础 处置，并对苯的毒性在老年人的影响。 苯的处置随着年龄的增长而改变，因为老年小鼠似乎 保持一定量的苯。 基于生理学的 苯处置的药代动力学模型表明， 改变可能是由于总苯代谢的变化或 苯的吸收。 这些模型预测的验证是 正在接受调查

The elderly represent a special population who are often at increased risk for susceptibility to the toxic effects of environmental agents. Alterations in disposition and/or biotransformation of xenobiotics in aged subjects may be a contributing factor to this enhanced susceptibility. In this laboratory, work is focused on alterations occurring with age in absorption, distribution, metabolism, and excretion of environmental toxicants, using two rodent models of aging. Benzene is a widespread environmental contaminant and human carcinogen whose disposition and toxicity has not been previously assessed in elderly subjects. Disposition and metabolism of benzene were examined in aged mice at 10 and 200 mg/kg. In addition, a physiologically based pharmacokinetic model was used to gain further insight into the basis of age-related differences in benzene disposition, and implications for toxicity of benzene in older subjects. Disposition of benzene was altered with age, in that older mice appeared to retain more of a given dose of benzene. Physiologically based pharmacokinetic modeling of benzene disposition suggested that this alteration could be due to changes in total benzene metabolism or in absorption of benzene. Verification of these model predictions is currently under investigation.