期刊
EXPERIMENTAL GERONTOLOGY
卷 39, 期 10, 页码 1521-1525出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2004.08.009
关键词
Forkhead; p21; p27; p53; Sir2
资金
- NIA NIH HHS [AG18780] Funding Source: Medline
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据