Abstract
The risk of developing neurodegenerative disorders such as Alzheimer's disease (AD) increases dramatically with age. Understanding the underlying mechanisms of brain aging is crucial for developing preventative and/or therapeutic approaches for age-associated neurological diseases. Recently, it has been suggested that epigenetic factors, such as histone modifications, maybe be involved in brain aging and age-related neurodegenerations. In this study, we investigated 14 histone modifications in brains of a cohort of young (3 months), old (22 months), and old age-matched dietary restricted (DR) and rapamycin treated BALB/c mice. Results showed that 7 out of all measured histone markers were changed drastically with age. Intriguingly, histone methylations in brain tissues, including H3K27me3, H3R2me2, H3K79me3 and H4K20me2 tend to disappear with age but can be partially restored by both DR and rapamycin treatment. However, both DR and rapamycin treatment also have a significant impact on several other histone modifications such as H3K27ac, H4K16ac, H4R3me2, and H3K56ac, which do not change as animal ages. This study provides the first evidence that a broad spectrum of histone modifications may be involved in brain aging. Besides, this study suggests that both DR and rapamycin may slow aging process in mouse brain via these underlying epigenetic mechanisms.
Highlights
In industrialized countries, life expectancy is rapidly rising, and this has led to an increasing incidence of agerelated neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson disease (PD) and Huntington Disease (HD)
Both dietary restricted (DR) and rapamycin treatment prevented the age-induced losses of H3K27me3, H3R2me2 and H3K79me3
Recent work suggests that histone acetylation has a critical role in age-associated declines in cognitive functions
Summary
Life expectancy is rapidly rising, and this has led to an increasing incidence of agerelated neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson disease (PD) and Huntington Disease (HD). Developing preventative or therapeutic interventions for such conditions demands deeper understanding of the processes underlying normal brain aging [1,2]. Brain aging is marked by a gradual decline in cognitive function, which is often correlated with age-dependent deterioration of synaptic function in brain regions crucial for memory formation and consolidation, such as the hippocampus and prefrontal cortex [3,4]. The neurobiological processes underlying these age-related learning and memory deficits include aberrant changes in gene transcription that eventually affects the plasticity of the aged brain. Changes in gene expression in neurons were thought to take place during www.impactjournals.com/oncotarget brain aging, and analysis of regions of the hippocampus and front cortex by microarray has confirmed this [5,6,7]. The molecular mechanisms underlying these changes in gene expression and the regulation are largely unknown, but recent studies point to a novel possibility that the dysregulation of epigenetic control of gene expression may be involved [8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
