SENESCENCE OF HUMAN ADRENAL CELLS

细胞衰老对于体内衰老的意义尚不清楚。 清楚 最近在更好地了解 正常人类细胞通过分子机制实现终末 非复制状态的培养提供了新的分子工具， 用于分析这种状态在体内组织中的意义。 在 这个项目，肾上腺皮质的细胞，这是以前被 关于细胞衰老的良好表征，将用于 调查这种关系。 1.肾上腺皮质再生和连续性的体内模型 建立传代以确定正常肾上腺皮质细胞是否 三个物种（人类，牛和老鼠）可以耗尽他们的能量。 在该体内模型中的增殖潜力，并比较 肾上腺皮质细胞在体内的增殖潜力， 培养中的增殖潜力。 2.因为端粒长度似乎提供了一个很好的指标， 培养物和体内细胞的增殖年龄，将进行测定。 进行，以确定端粒长度的变化是否类似于 肾上腺细胞在体内和细胞中最大传代次数 在文化中。 3.根据对人、牛和大鼠肾上腺皮质 细胞通常不表达p21衰老细胞衍生抑制剂（SDI 1） 在体内，但是当转移到培养物中时快速诱导该基因 环境，实验将进行调查的功能 p21/Sdi 1在体外培养肾上腺皮质细胞中表达及其对肾上腺皮质细胞增殖的影响 细胞增殖 4.实验将进行调查的原因高 培养的肾上腺皮质细胞中p21/Sdi 1表达水平。 5.因为p21 Sdi 1是迄今为止唯一一个被鉴定出的蛋白质， 有理由相信它在衰老细胞中的表达是导致衰老的原因， 而不是关于非分裂状态的关联，它是 研究p21/Sdi 1在大肠癌中的表达和功能状态是非常重要的。 在体内最大限度传代的细胞，并将其与 在通过分裂达到非分裂状态的细胞中， 文化

The significance of cellular senescence for in vivo aging is not yet clear. The recent development of a greater understanding of the molecular mechanisms by which normal human cells achieve a terminally nonreplicating state in culture has provided new molecular tools required for an analysis of the significance of this state in tissues in vivo. In this Project, the cells of the adrenal cortex, which have previously been well characterized with respect to cellular senescence, will be used to investigate this relationship. 1. An in vivo model of adrenocortical regeneration and continuous passaging will be set up to establish whether normal adrenocortical cells from three species (human, bovine, and rat) can exhaust their proliferative potential in this in vivo model and to compare the proliferative potential of adrenocortical cells in vivo with their proliferative potential in culture. 2. Because telomere length appears to provide a good indicator of the proliferative age of cells in culture and in vivo, assays will be performed to establish whether changes in telomere length are similar in adrenal cells passaged maximally in vivo and in cells passaged maximally in culture. 3. Based on the observation that human, bovine, and rat adrenocortical cells do not normally express p21 senescent cell derived inhibitor (SDI1) in vivo, yet rapidly induce this gene when transferred to the culture environment, experiments will be performed to investigate the functional status of p21/Sdi1 in adrenocortical cells in culture and its effects on cell proliferation. 4. Experiments will be performed to investigate the cause of the high level of p21/Sdi1 expression in adrenocortical cells in culture. 5. Because p21Sdi1 is the only protein yet identified for which there is reason to believe that its expression in senescent cells is causative rather than associative with respect to the nondividing state, it is important to examine the expression and functional state of p21/Sdi1 in cells which have been maximally passaged in vivo and to compare it to that in cells that have reached the nondividing state by division in culture.