BIOMARKERS OF AGING--CIRCULATING/DEPOSITED OSTEOCALCIN

骨钙素（OC）是一种维生素K依赖性蛋白质， 尤其是成骨细胞。 新的主要部分 合成的OC沉积在骨中;然而， 量被释放到循环中，并最终在 肾 循环部分提供了OC的测量 骨合成和成骨细胞对激素的反应 和其他代理人。 OC目前在临床上用于监测 成骨细胞功能和骨转换的变化， 用于评估实验性治疗在 治疗骨质疏松症和其他骨疾病。 以来 骨钙素提供了骨代谢的量度， 血清OC水平似乎与年龄有关， 反映了随年龄增长而发生的骨生理变化。 老化的啮齿动物群体作为老化的资源 NIA的研究将测试血清中 骨钙素作为年龄和饮食限制的函数， 是否存在急性和慢性给药 促钙激素、PTH、降钙素和维生素D 代谢产物1，25（OH）2D 3。 大鼠放射免疫测定 骨钙素已经在我们的实验室和放射免疫测定， 小鼠骨钙素正在开发中。 血清骨钙素将 与骨钙素mRNA的转录水平相关， 骨钙素的合成。 维生素K的总体状况 通过检查大鼠尿中游离4- 羧基谷氨酸 骨沉积的骨钙素最初没有糖化 （非酶促糖基化），但随着时间的推移变成糖化。 我们已经在人体中证明， 骨钙素在儿童中是低的，在成人中相当稳定，但迅速 随着新骨合成的减少和年龄的增加， 骨积聚。 糖化骨钙素的测定 也应该是一个有价值的衰老生物标志物。 其内容 将评价与总骨骨钙素和骨 密度（矿物质）在雄性和雌性老龄大鼠。

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.