Increased nuclear proteins in muscle satellite cells in aged animals as compared to young growing animals
Increased nuclear proteins in muscle satellite cells in aged animals as compared to young growing animals
复制标题
DOI：
10.1016/j.exger.2004.08.009
复制
发表时间：
2004-10-01
影响因子：
3.9
通讯作者：
Booth, FW
中科院分区：
文献类型：
--
作者：
Machida, S;Booth, FW
有证据表明，卫星细胞可能在进行修复或维持质量的老化肌肉中发挥一些限制作用，这是潜在的临床问题，因为这可能导致肌肉减少症。此外，有关老年动物中大鼠卫星细胞增殖较低的细胞机制的信息不足。因此，假设以下蛋白质将在来自老年大鼠骨骼肌的卫星细胞核中增加：细胞周期蛋白依赖性激酶（CDK）抑制剂p21（WAF 1/CIP 1）和P27（Kip 1）以及转录因子p53和Forkhead box，亚群O 1（FOXO 1）。此外，NAD+依赖性组蛋白去乙酰化酶SIRT 1，酵母SIR 2（沉默信息调节因子2）的哺乳动物直系同源物和Sirtuin家族的成员，被假设为减少老年大鼠的卫星细胞核。老年卫星细胞（30个月大）表现出较少数量的BrdU阳性细胞相比，卫星细胞（3个月大）从年轻的生长动物。Western blot分析表明，老年卫星细胞的细胞核积累的细胞周期抑制剂p21（WAF 1/CIP 1）和p27。此外，核p53和FOXO I蛋白也较高的老卫星细胞比年轻的生长动物的细胞。这些数据表明，p53/p21（WAF 1/CIP 1）和FOXO 1/p27（Kip 1）依赖的途径可能有助于与年龄相关的卫星细胞增殖的减少。细胞质锰超氧化物歧化酶（MnSOD），FOXO 1驱动的基因，是较高的老卫星细胞。出乎意料的是，与年轻生长动物的卫星细胞相比，老年卫星细胞的核SIRT 1也增加了。在老年卫星细胞中，核SIRT 1表达增强的生理意义目前仍然难以捉摸。总之，与年轻的生长中的动物相比，老年大鼠的卫星细胞具有抑制细胞周期的蛋白质的核积累。(C)2004年爱思唯尔公司All rights reserved.
Evidence implies that satellite cells could play some limiting role in aged Muscle undergoing repair or maintenance of mass, which is of potential clinical concern as this could contribute to sarcopenia. Further, insufficient information is available concerning the cellular mechanisms responsible for the lower rat satellite cell proliferation in old animals. Thus, it was hypothesized that the following proteins would be increased in nuclei of satellite cells from old rat skeletal muscle: the cyclin-dependent kinase (CDK) inhibitors p21(WAF1/CIP1) and P27(Kip1) as well as the transcription factors p53 and Forkhead box, subgroup O1 (FOXO1). In addition, the NAD+-dependent histone deacetylase SIRT1, the mammalian ortholog of the yeast SIR2 (silence information regulator 2) and a member of the Sirtuin family, was hypothesized to decrease in satellite cell nuclei of old rats. Old satellite cells (30-months old) exhibited a lesser number of BrdU-positive cells as compared to satellite cells (3-months old) from young growing animals. Western blot analysis demonstrated that nuclei of old satellite cells accumulated the cell cycle inhibitors p21(WAF1/CIP1) and p27. In addition, nuclear p53 and FOXO I proteins were also higher in old satellite cells than in cells from young growing animals. These data indicated both p53/p21(WAF1/CIP1) and FOXO1/p27(Kip1)-dependent pathways might contribute to the age-associated decrease in satellite cell proliferation. Cytoplasmic manganese superoxide dismutase (MnSOD), a gene driven by FOXO1, was higher in old satellite cells. Unexpectedly, nuclear SIRT1 was also increased in old satellite cells compared with satellite cells from young growing animals. The physiological significance of enhanced nuclear SIRT1 expression in old satellite cells remains elusive at this time. In summary, satellite cells in old rats have nuclear accumulation of proteins inhibiting the cell cycle as compared to young, growing animals. (C) 2004 Elsevier Inc. All rights reserved.