Abstract：
BRG1 (Brahma-related gene 1) is a member of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling complex which utilizes the energy from ATP hydrolysis for its activity. In addition to its role of regulating the expression of a vast array of genes, BRG1 mediates DNA repair upon genotoxic stress and regulates senescence. During organismal ageing, there is accumulation of unrepaired/unrepairable DNA damage due to progressive breakdown of the DNA repair machinery. The present study investigates the expression level of BRG1 as a function of age in the liver of 5- and 21-month-old female mice. It also explores the impact of dietary restriction on BRG1 expression in the old (21-month) mice. Salient findings of the study are: Real-time PCR and Western blot analyses reveal that BRG1 levels are higher in 5-month-old mice but decrease significantly with age. Dietary restriction increases BRG1 expression in the 21-month-old mice, nearly restoring it to the level observed in the younger group. Similar expression patterns are observed for DNA damage response genes ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad3-related) with the advancement in age and which appears to be modulated by dietary restriction. BRG1 transcriptionally regulates ATM as a function of age and dietary restriction. These results suggest that BRG1, ATM and ATR are downregulated as mice age, and dietary restriction can restore their expression. This implies that dietary restriction may play a crucial role in regulating BRG1 and related gene expression, potentially maintaining liver repair and metabolic processes as mice age.
摘要：
BRG1（Brahma相关基因1）是SWI/SNF（开关/蔗糖不可发酵）染色质重塑复合物的成员，该复合物利用ATP水解的能量进行活性。除了其调控大量基因表达的作用外，BRG1在基因毒性胁迫下介导DNA修复并调节衰老。在有机体老化期间，由于DNA修复机制的进行性破坏,存在未修复/不可修复的DNA损伤的累积。本研究调查了5个月和21个月大的雌性小鼠肝脏中BRG1的表达水平随年龄的变化。它还探讨了饮食限制对老年（21个月）小鼠BRG1表达的影响。该研究的主要发现是：实时PCR和蛋白质印迹分析显示，5月龄小鼠的BRG1水平较高，但随着年龄的增长显着降低。饮食限制增加21月龄小鼠的BRG1表达，几乎将其恢复到年轻群体中观察到的水平。随着年龄的增长，DNA损伤反应基因ATM（共济失调毛细血管扩张突变）和ATR（共济失调毛细血管扩张和Rad3相关）观察到类似的表达模式，并且似乎受到饮食限制的调节。BRG1转录调节ATM作为年龄和饮食限制的功能。这些结果表明，BRG1，ATM和ATR随着小鼠年龄的增长而下调，限制饮食可以恢复他们的表达。这意味着饮食限制可能在调节BRG1和相关基因表达中起关键作用。随着小鼠年龄的增长，可能维持肝脏修复和代谢过程。
