BIOMARKERS OF AGING--CIRCULATING/DEPOSITED OSTEOCALCIN

骨钙素(OC)是一种依赖维生素K的蛋白质 尤其是成骨细胞。新能源的大部分 合成的OC沉积在骨中；然而，成比例的 数量被释放到循环中，最终在 肾脏。循环部分提供OC的量度 骨合成与成骨细胞对激素的反应 和其他特工。OC目前在临床上用于监测 成骨细胞功能和骨转换的变化 有助于评估实验性治疗的效果 治疗骨质疏松症和其他骨病。自.以来 骨钙素提供了一种衡量骨骼代谢的指标，因为 血清水平似乎与年龄有关，很可能血清OCS 反映伴随年龄增长的骨骼生理变化。 老化的啮齿动物群体被维持为老化的来源 NIA的研究将测试血清的变化 骨钙素作为年龄和饮食限制的函数以及在 有或没有急性和慢性给药 促降钙素、甲状旁腺素、降钙素和维生素D 代谢物1，25(OH)2D3。大鼠的放射免疫测定 骨钙素已经在我们的实验室进行了操作，并进行了放射免疫分析 小鼠骨钙素正在开发中。血清骨钙素将 与骨钙素mRNA和骨钙素基因转录水平相关 骨钙素在骨骼中的合成。儿童的整体维生素K状况 将通过检测尿液中游离4-氨基丁酸的排出量来监测大鼠。 羧基谷氨酸。 骨沉积骨钙素最初是不糖化的 (非酶糖基化)，但随时间糖化。 我们已经在人类身上证明了糖链的作用 骨钙素在儿童中含量较低，在成人中相当稳定，但很快 随着新骨合成的减少和年龄的增加，老年人的新骨合成增加 骨头会堆积起来。糖化骨钙素的测定 也应该作为衰老的一个有价值的生物标志物。它的内容 将根据总骨、骨钙素和骨量进行评估 雄性和雌性衰老大鼠的密度(矿物质)。

Osteocalcin (OC), a vitamin K-dependent protein is made specifically by osteoblasts. The major portion of newly synthesized OC is deposited in bone; however, a proportional amount is released into the circulation and finally degraded in the kidney. The circulating portion provides a measure of OC synthesis in bone and of the response of osteoblasts to hormones and other agents. OC is currently used clinically to monitor changes in osteoblast function and bone turnover and has been useful in evaluating the effect of experimental therapies in the treatment of osteoporosis and other bone disorders. Since osteocalcin provides a measure of bone metabolism and since serum levels appear to be aged related, it is likely that serum OCs reflect bone physiologic changes that are concomitants of aging. The aging rodent colonies maintained as a resource for aging research by the NIA will be tested for changes in serum osteocalcin as a function of age and diet restriction and in the presence or absence of acute and chronic administration of the calcitropic hormones, PTH, calcitonin and the vitamin D metabolite 1,25(OH)2D3. The RIA measurement for rat osteocalcin is already operative in our laboratory and an RIA for mouse osteocalcin is under development. Serum osteocalcin will be correlated with transcriptional levels of osteocalcin mRNA and osteocalcin synthesis in bone. The overall vitamin K status of the rats will be monitored by examining the urinary ouput of free 4- carboxyglutamic acid. Bone deposited osteocalcin is initially free of glycation (nonenzymatic glycosylation) but becomes glycated with time. We have already shown in humans that the glycatation of osteocalcin is low in children, fairly constant in adults, but rapidly increases in the elderly as new bone synthesis decreases and older bone accumulates. The measurement of glycated osteocalcin should also serve as a valuable biomarker of aging. Its content will be evaluated in relation to total bone osteocalcin and bone density (mineral) in male and female aging rats.