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首页> 外文期刊>Journal of anti-aging medicine >Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo.
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Telomeres Shorten with Age in Rat Cerebellum and Cortex in vivo.

机译：在体内大鼠小脑和皮质中端粒会随着年龄的增长而缩短。

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Normal somatic cells have a finite replicative capacity. With each cell division, telomeres, the ends of linear chromosomes, progressively shorten until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell type in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. Previous research in our laboratory has found that telomeres shorten in rat microglia with increasing time in vitro. Our current hypothesis is that telomeres shorten in rat brain in vivo with increasing age. Tissue samples of cerebellum and cortex were obtained from Sprague-Dawley rats of various ages. Genomic DNA and total protein was isolated from each sample for telomere length measurement via Southern blot analysis (up to 5 months) and telomerase activity measurement via TRAP analysis (up to 6 months), respectively. Telomere shortening occurs in vivo in both rat cerebellum and cortex from day 21 to approximately 5 months of age. Cortex samples possessed shorter telomeres than did cerebellum samples. The longest telomeres undergo the most dramatic shortening, while the shortest telomeres exhibit only slight attrition. Telomerase activity slowly increases from day 21 to approximately 6 months of age, with the cerebellum exhibiting higher activity than cortex in all instances. These results indicate that telomere shortening occurs in rat brain in vivo with increasing age, and that the low levels of telomerase activity present may be preferentially recruited to maintain the shortest telomeres while allowing the longer ones to shorten more rapidly. Since microglia are thought to be the only mature cells of the postnatal CNS undergoing appreciable cell division, we propose that the telomere shortening occurring in the adult rat brain with age can be largely attributed to microglial cell division. Our findings provide an impetus to further investigate the pattern of telomere length and telomerase activity that emerges with further aging in the rat brain.
机译：正常的体细胞具有有限的复制能力。随着每个细胞分裂，端粒（线性染色体的末端）逐渐缩短，直到达到临界长度，此时细胞进入复制性衰老。一些细胞通过端粒酶的作用维持其端粒。胶质细胞，特别是小胶质细胞，是中枢神经系统（CNS）中唯一显示出明显有丝分裂潜能的成年细胞类型，因此容易发生端粒缩短。我们实验室先前的研究发现端粒在大鼠小胶质细胞中会随着体外时间的增加而缩短。我们目前的假设是端粒在大鼠脑内随着年龄的增长而缩短。从不同年龄的Sprague-Dawley大鼠获得小脑和皮质的组织样品。从每个样品中分离基因组DNA和总蛋白，分别通过Southern印迹分析（长达5个月）和TRAP分析（长达6个月）测量端粒长度。从第21天到大约5个月大，大鼠小脑和皮层体内都发生端粒缩短。皮质样品具有比小脑样品短的端粒。最长的端粒经历最剧烈的缩短，而最短的端粒仅表现出轻微的磨损。从第21天到大约6个月大，端粒酶活性缓慢增加，在所有情况下小脑均表现出比皮质更高的活性。这些结果表明端粒缩短在大鼠脑中随年龄的增长而发生，并且存在的端粒酶活性低水平可优先招募以维持最短的端粒，同时允许更长的端粒更快地缩短。由于小胶质细胞被认为是产后中枢神经系统中唯一经历成熟细胞分裂的成熟细胞，因此我们提出，成年大鼠大脑中随年龄增长而发生的端粒缩短主要归因于小胶质细胞分裂。我们的发现为进一步研究端粒长度和端粒酶活性的模式提供了动力，端粒长度和端粒酶活性随着大鼠大脑的进一步老化而出现。

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