GSE115437 HDAC1 modulates OGG1-initiated oxidative DNA damage repair, brain aging, and Alzheimer ’s disease pathology

Contributors : Ping-Chieh Pao ; Fan Gao ; Li-Huei Tsai ; Hugh P CamSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusUnrepaired DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair activity to stave off age-associated functional decline remain obscure. Here, we show that histone deacetylase 1 (HDAC1) modulates DNA repair in the aging brain via targeting OGG1 of the base excision repair pathway. Mice deficient in HDAC1 display age-associated accumulation of DNA damage in the brain and cognitive impairment. HDAC1 interacts with and positively stimulates OGG1, a DNA glycosylase that primarily acts on 8-oxoguanine (8-oxoG), a type of oxidative DNA damage associated with transcriptional repression. Loss of HDAC1 leads to impaired OGG1 activity, 8-oxoG accumulation at the promoters of a subset of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG lesions along with reduced HDAC1 activity and downregulation of a similar set genes in the 5XFAD mouse model of Alzheimer ’s disease (AD). Notably, pharmacological activation of HDAC1 confers protection against the deleterious effects of 8-oxoG lesions in the brains of aged wild-type and 5XFAD mice. Our work uncovers an important role for HDAC1 in the repair of 8-oxoG lesions and highlights HDAC1 activation as a nove l ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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A fair amount of effort is presently put towards the exploration of supplements derived from vitamin B3 compounds (nicotinamide, niacin, nicotinamide riboside) that act as precursors to enable the manufacture of nicotinamide adenine dinucleotide (NAD). NAD is an important component in mitochondrial activity, and levels decline with age. Some portion of the loss of mitochondrial function, implicated in the progression of many age-related conditions, is due to NAD insufficiency. There is a rich history of the use of high doses of vitamin B3 as an intervention, most of it predating modern understanding of the role of NAD in m...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
HDAC1 is involved in a form of DNA repair, but levels decline with age, as well as in Alzheimer's disease. This leads to a greater accumulation of unrepaired oxidative DNA damage in neurons. Researchers here note that increased activation of HDAC1 appears to improve cognitive function via a reduction in this oxidative DNA damage. An HDAC1 activator drug has been tested as a treatment for dementia, but caused serious side-effects. Better compounds or other approaches may be able to obtain similar benefits without the harms. There are several members of the HDAC family of enzymes, and their primary function is to m...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function. On Nutraceutical Senolytics https://www.fightaging.org/archives/2020/05/on-nutraceutical-senolytics/ Nutraceuticals are compounds derived from foods, usually plants. In principle one can find useful therapies in the natural world, taking the approach of identifying interesting molecules and refining them to a greater potency than naturally occurs in order to produce a usefully large therape...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we found that older nematodes have higher ROS levels. Interestingly, after hydrogen treatment, the ROS levels were significantly decreased, and hydrogen could significantly extend the lifespans of the N2, sod-3 and sod-5 mutant strains, by approximately 22.7%, 9.5%, and 8.7%, respectively. In addition, aging is regulated by a variety of pathways, such as the insulin signaling pathway, the rapamycin target signaling pathway, and the caloric restriction pathway. However, our results showed that the lifespans of the daf-2 and daf-16 strains, in which these pathways are upregulated, were not affected afte...
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(University of Virginia Health System) Focused ultrasound, the researchers hope, could revolutionize treatment for conditions from Alzheimer's to epilepsy to brain tumors -- and even help repair the devastating damage caused by stroke.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Abstract Increasing evidence indicates that lipid metabolism is disturbed in central nervous system (CNS) disorders, such as multiple sclerosis, Alzheimer's, and Parkinson's disease. Extracellular vesicles (EVs), including exosomes and microvesicles, are nanosized particles that play an essential role in intercellular communication and tissue homeostasis by transporting diverse biologically active molecules, including a large variety of lipid species. In the last decade, studies defined that changes in the EV lipidome closely correlate with disease-progression and -remission in CNS disorders. In this review, we su...
Source: Advanced Drug Delivery Reviews - Category: Drugs & Pharmacology Authors: Tags: Adv Drug Deliv Rev Source Type: research
In conclusion, our study demonstrated that Nrf2 deficiency promoted the increasing trend of autophagy during aging in skeletal muscle. Nrf2 deficiency and increasing age may cause excessive autophagy in skeletal muscle, which can be a potential mechanism for the development of sarcopenia. To What Degree is Chondrocyte Hypertrophy in Osteoarthritis Due to Cellular Senescence? https://www.fightaging.org/archives/2020/04/to-what-degree-is-chondrocyte-hypertrophy-in-osteoarthritis-due-to-cellular-senescence/ Senescent cells are large. They do not replicate, that function is disabled, but it is as if they go ...
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AbstractAlzheimer ’s disease (AD) is an incurable neurodegenerative disease that is more prevalent in women. The increased risk of AD in women is not well understood. It is well established that there are sex differences in metabolism and that metabolic alterations are an early component of AD. We utilized a cross- species approach to evaluate conserved metabolic alterations in the serum and brain of human AD subjects, two AD mouse models, a human cell line, and twoCaenorhabditis elegans AD strains. We found a mitochondrial complex I-specific impairment in cortical synaptic brain mitochondria in female, but not male,...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
In this study, the potentiating effect of sesamin, a major lignan in sesame seeds (Sesamum indicum) and oil, on NGF-induced neurogenesis and its involved mechanisms were firstly reported. Sesamin effectively enhanced the PC12 neuron-like cell differentiation and neurite length under insufficient conditions of NGF. The neuronal markers including synaptophysin and growth-associated protein-43 along with the synaptic connections were significantly increased in combination treatment between sesamin and NGF. Moreover, sesamin also increased the level of phospho-ERK1/2 and SIRT1 protein, an important regulatory protein of the ne...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
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