CHANGES IN CALCIUM AND VITAMIN D METABOLISM WITH AGE

许多对人类的研究表明，这种能力有所下降。 随着年龄的增长，肠道吸收钙(Ca)的能力下降。为了研究 钙吸收减少的机制及体内钙的变化 维生素D3的代谢随着年龄的增长，我们已经将大鼠发展成为一种动物 模特。我们已经证明，大鼠的钙离子随年龄增长而发生变化。 吸收和维生素D3代谢非常类似于 人类。此外，我们还开发了一种新技术，它使用孤立的 肾皮质切片用于研究1，25-(OH)2-D3的产生， 维生素D3的生物活性代谢物及其体外调节 在哺乳动物身上。因此，我们建议使用这种肾脏切片技术来 回答问题：“是什么机制导致了 肾脏1，25-(OH)2-D3的产生与年龄有关？“为了回答这个问题，我们 建议检验三个假说：a.1，25-(OH)2-D3 产生的原因是成人肾脏对 甲状旁腺素(PTH)。甲状旁腺素对肾脏的调节作用失败 1，25-(OH)2-D3的产生可能是由于年龄相关的一个或多个 以下肾脏成分：cAMP的产生和降解， CAMP依赖的蛋白激酶活性，以及肾脏蛋白的磷酸化。 B.缺钙期间1，25-(OH)2-D3的生成减少是由于 成虫对生物活性甲状旁腺素的分泌减少 CA剥夺。C.1，25-(OH)2-D3产量减少是由于 减少成人生长激素的产生或作用。通过测试 在上述假设的动物模型中，我们将确定其作用机制 对1，25-(OH)2-D产量随年龄增长而减少负责，这是 在老鼠和人类身上都可以看到。对这些机制的了解将表明 改善1，25-(OH)2-D产生、钙吸收和最终钙吸收的方法 老年人群的平衡与骨矿化。

Many studies in humans have shown that there is a decline in the capacity of the intestine to absorb calcium (Ca) with increasing age. To study the mechanisms responsible for the decrease in Ca absorption and changes in vitamin D3 metabolism with age, we have developed the rat as an animal model. We have shown that the rat demonstrates age-related changes in Ca absorption and vitamin D3 metabolism that are very similar to those seen in humans. In addition, we have developed a new technique that uses isolated renal cortical slices to study production of 1,25-(OH)2-D3, the biologically active metabolite of vitamin D3, and its regulation in vitro in the mammal. Therefore, we propose to use this renal slice technique to answer the question "What is the mechanism responsible for the decrease in renal 1,25-(OH)2-D3 production with age?" To answer this question, we propose to test three hypotheses: a. The decreased 1,25-(OH)2-D3 production is due to a decreased responsiveness of the adult kidney to parathyroid hormone (PTH). This failure of PTH to modulate renal 1,25-(OH)2-D3 production may be due to age-related changes in one or more of the following renal components: cAMP production and degradation, cAMP-dependent protein kinase activity, and renal protein phosphorylation. b. The decreased 1,25-(OH)2-D3 production during Ca deprivation is due to decreased secretion of biologically active PTH by the adult in response to Ca deprivation. c. The decreased 1,25-(OH)2-D3 production is due to decrease production or action of growth hormone in the adult. By testing the above hypotheses in an animal model, we will determine the mechanisms responsible for the decreased 1,25-(OH)2-D production with age, which is seen in both rat and human. Knowledge of these mechanisms will suggest ways of improving 1,25-(OH)2-D production, Ca absorption, and ultimately Ca balance and bone mineralization in the elderly population.