Gene regulation and DNA damage in the ageing human brain

@article{Lu2004GeneRA,
  title={Gene regulation and DNA damage in the ageing human brain},
  author={Tao Lu and Ying Pan and S Y Kao and Cheng Li and Isaac S. Kohane and Jennifer Chan and Bruce A. Yankner},
  journal={Nature},
  year={2004},
  volume={429},
  pages={883-891}
}
The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by… Expand
Regulation of the cognitive aging process by the transcriptional repressor RP58
Aging involves a decline in physiology which is a natural event in all living organisms. An accumulation of DNA damage contributes to the progression of aging. DNA is continually damaged by exogenousExpand
Gene expression in the aging human brain: an overview
TLDR
Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. Expand
A review and appraisal of the DNA damage theory of ageing.
TLDR
A major role of DNA damage in the modulation of longevity is suggested, possibly through effects on cell dysfunction and loss, although understanding how to modify DNA damage repair and response systems to delay ageing remains a crucial challenge. Expand
Sixty years old is the breakpoint of human frontal cortex aging
TLDR
It is suggested that the deterioration in oxidative stress homeostasis during aging induces an adaptive response of stress resistance mechanisms based on the sustained expression of REST, and increased or decreased expression of Akt and mTOR, respectively, over the adult lifespan in order to preserve cell neural survival and function. Expand
REST and Stress Resistance in Aging and Alzheimer’s Disease
TLDR
It is shown that induction of the repressor element 1-silencing transcription factor (REST) is a universal feature of normal ageing in human cortical and hippocampal neurons, and levels during ageing are closely correlated with cognitive preservation and longevity. Expand
Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function
  • E. Englander
  • Medicine, Biology
  • Mechanisms of Ageing and Development
  • 2008
TLDR
Analysis of evidences for brain levels and activities of the base excision repair (BER) pathway in the context of newly available, comprehensive in situ hybridization analyses of genes encoding repair enzymes suggest that not all subsets of BER are equally represented in the brain. Expand
DNA polymerase β deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes
TLDR
It is demonstrated that a modest decrement in base excision repair capacity can render the brain more vulnerable to AD-related molecular and cellular alterations. Expand
Evolution of the Aging Brain Transcriptome and Synaptic Regulation
TLDR
Repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes. Expand
Lymphocytes of Patients with Alzheimer’s Disease Display Different DNA Damage Repair Kinetics and Expression Profiles of DNA Repair and Stress Response Genes
TLDR
It is found that kinetics of the stress response in the DNA were significantly different in AD patients, supporting the hypothesis that repair pathways may be compromised in AD and that peripheral lymphocytes can reveal this condition. Expand
Chromatin regulation of DNA damage repair and genome integrity in the central nervous system.
TLDR
The sources and types of DNA damage and the relevant repair pathways in the nervous system are introduced and the chromatin regulation of these processes are discussed and the contribution of genomic instability to neurodegenerative diseases is summarized. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 26 REFERENCES
Gene-expression profile of the ageing brain in mice
TLDR
Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses, which resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions. Expand
The effects of aging on gene expression in the hypothalamus and cortex of mice.
TLDR
Differences in gene expression in the hypothalamus and cortex of young and aged mice are examined by using high-density oligonucleotide arrays to identify key genes involved in neuronal structure and signaling and suggest their roles in learning and memory. Expand
Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain
TLDR
Results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected and it is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases. Expand
Gene Microarrays in Hippocampal Aging: Statistical Profiling Identifies Novel Processes Correlated with Cognitive Impairment
TLDR
A new integrative model of brain aging is suggested in which genomic alterations in early adulthood initiate interacting cascades of decreased signaling and synaptic plasticity in neurons, extracellular changes, and increased myelin turnover-fueled inflammation in glia that cumulatively induce aging-related cognitive impairment. Expand
Gene expression profiling in Werner syndrome closely resembles that of normal aging
TLDR
It is proposed that a defect in the transcription of the genes as identified in this study could produce many of the complex clinical features of WS, and supports the use of WS as an aging model and implies that the transcription alterations common to WS and normal aging represent general events in the aging process. Expand
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
TLDR
The findings suggest that the insulin/IGF-I pathway ultimately exerts its effect on lifespan by upregulating a wide variety of genes, including cellular stress-response, antimicrobial and metabolic genes, and by downregulating specific life-shortening genes. Expand
Effect of oxidative DNA damage in promoter elements on transcription factor binding.
TLDR
It is concluded that minor alterations in base composition at a crucial position within some, but not all, promoter elements have the ability to disrupt transcription factor binding. Expand
Development and field-test validation of an assay for DNA repair in circulating human lymphocytes.
TLDR
The preliminary identification of a specific subset at risk for basal cell carcinoma patients and cancer-free controls as a consequence of significant reduction to the repair of photochemically (UV)-damaged plasmid DNA is led to. Expand
Genetics and the Specificity of the Aging Process
TLDR
The aging process may be more specific than previously anticipated on evolutionary grounds because the biology of reactive oxygen species in the mitochondria and elsewhere might be the main determinant of life-span in this organism. Expand
Dopamine-dependent neurotoxicity of α-synuclein: A mechanism for selective neurodegeneration in Parkinson disease
TLDR
It is shown that accumulation of α-synuclein in cultured human dopaminergic neurons results in apoptosis that requires endogenous dopamine production and is mediated by reactive oxygen species. Expand
...
1
2
3
...