Neuroprotection against Amyloid- β-Induced DNA Double-Strand Breaks Is Mediated by Multiple Retinoic Acid-Dependent Pathways.

In this study, we have investigated the role of all-trans-retinoic acid (RA) as a neuroprotective agent against Aβ 1-42-induced DNA double-strand breaks (DSBs) in neuronal SH-SY5Y and astrocytic DI TNC1 cell lines and in murine brain tissues, by single-cell gel electrophoresis. We showed that RA does not only repair Aβ 1-42-induced DSBs, as already known, but also prevents their occurrence. This effect is independent of that of other antioxidants studied, such as vitamin C, and appears to be mediated, at least in part, by changes in expression, not of the RARα, but of the PPARβ/δ and of antiamyloidogenic proteins, such as ADAM10, implying a decreased production of endogenous Aβ. Whereas Aβ 1-42 needs transcription and translation for DSB production, RA protects against Aβ 1-42-induced DSBs at the posttranslational level through both the RARα/β/γ and PPARβ/δ receptors as demonstrated by using specific antagonists. Furthermore, it could be shown by a proximity ligation assay that the PPARβ/δ-RXR interactions, not the RARα/β/γ-RXR interactions, increased in the cells when a 10 min RA treatment was followed by a 20 min Aβ 1-42 treatment. Thus, the PPARβ/δ receptor, known for its antiapoptotic function, might for these short-time treatments play a role in neuroprotection via PPARβ/δ-RXR heterodimerization and possibly expression of antiamyloido...
Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research

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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...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
(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 ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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
In conclusion, elevated brain amyloid was associated with family history and APOE ε4 allele but not with multiple other previously reported risk factors for AD. Elevated amyloid was associated with lower test performance results and increased reports of subtle recent declines in daily cognitive function. These results support the hypothesis that elevated amyloid represents an early stage in the Alzheimer's continuum. Blood Metabolites as a Marker of Frailty https://www.fightaging.org/archives/2020/04/blood-metabolites-as-a-marker-of-frailty/ Frailty in older people is usually diagnosed in a sympt...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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