Pynskhem Bok Swer, Babiangshisha Kharbuli, Donkupar Syiem, Ramesh Sharma
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引用次数: 0
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.
期刊介绍:
The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments.
Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.