Epigenome-wide association study of alcohol consumption in N  = 8161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine/glutamate transporter SLC7A11 as a top target

Mol Psychiatry. 2021 Dec 2. doi: 10.1038/s41380-021-01378-6. Online ahead of print.ABSTRACTAlcohol misuse is common in many societies worldwide and is associated with extensive morbidity and mortality, often leading to alcohol use disorders (AUD) and alcohol-related end-organ damage. The underlying mechanisms contributing to the development of AUD are largely unknown; however, growing evidence suggests that alcohol consumption is strongly associated with alterations in DNA methylation. Identification of alcohol-associated methylomic variation might provide novel insights into pathophysiology and novel treatment targets for AUD. Here we performed the largest single-cohort epigenome-wide association study (EWAS) of alcohol consumption to date (N = 8161) and cross-validated findings in AUD populations with relevant endophenotypes, as well as alcohol-related animal models. Results showed 2504 CpGs significantly associated with alcohol consumption (Bonferroni p value
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research

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In this study, they found these drugs can kill senescent cells from cultures of human fat tissue. The tissue was donated by individuals with obesity who were known to have metabolic troubles. Without treatment, the human fat tissues induced metabolic problems in immune-deficient mice. After treatment with dasatinib and quercetin, the harmful effects of the fat tissue were almost eliminated. Targeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2...
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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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This article will review the relationship between diabetes mellitus and AD as it relates to tau pathology. More understanding of the link between diabetes mellitus and AD could change the approach researchers and clinicians take toward both diseases, potentially leading to new treatments and preventative strategies in the future. Signaling from White Fat Tissue Contributes to Age-Related Hair Follicle Dysfunction https://www.fightaging.org/archives/2021/11/signaling-from-white-fat-tissue-contributes-to-age-related-hair-follicle-dysfunction/ Changes in fat tissue behavior in the skin take place with age, ...
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In conclusion, in less common and visible cardiovascular diseases, it is crucial to recognize substantial progress and achievement, given that penetration of such information into clinical practice and the patient community can be inconsistent. Diseases such as hypertrophic cardiomyopathy, pulmonary arterial hypertension, and ATTR cardiac amyloidosis, once linked to a uniformly adverse prognosis, are now associated with the opportunity for patients to experience satisfactory quality of life and extended longevity. VitaDAO, a Novel Approach to Crowdfunding Life Science Research https://www.fightaging.org/archive...
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In conclusion, this study examined how age and the process of aging are associated with changes in the microbiome of the small intestine, using validated sampling and processing techniques. The most significant differences are higher relative abundance of the phylum Proteobacteria and decreased relative abundance of Bacteroidetes in older subjects when compared to the youngest group. The higher relative abundance of Proteobacteria appeared to affect other duodenal microbial taxa, leading to decreased microbial diversity and increased relative abundance of coliforms and of anaerobic bacteria. The small intestine is vital to...
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In conclusion, cancer survivors, especially older individuals, demonstrate greater odds of and accelerated functional decline, suggesting that cancer and/or its treatment may alter aging trajectories. Linking Particulate Air Pollution and Dementia in a Small Region of the US https://www.fightaging.org/archives/2021/08/linking-particulate-air-pollution-and-dementia-in-a-small-region-of-the-us/ It is fairly settled that evident particulate air pollution, such as daily exposure to smoke from wood-fueled cooking fires, has a strongly detrimental effect on long-term health. The mechanisms involved are inflamm...
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In conclusion, iMSC-sEVs could rejuvenate the senescence of NPCs and attenuate the development of IVDD. Cell Signaling via Exosomes in the Development of Vascular Calcification https://www.fightaging.org/archives/2021/05/cell-signaling-via-exosomes-in-the-development-of-vascular-calcification/ Vascular calcification is a feature of aging, a process in which cells in the blood vessel wall take on inappropriate identities and activities that are more appropriate to bone tissue. Evidence of recent years implicates chronic inflammation and the presence of senescent cells in this process. Senescent cells caus...
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In conclusion, we showed that addition of resistance exercise training, but not dietary EAAs, to the myostatin inhibition further increased muscle mass through the attenuation of muscle protein breakdown with proportionate improvements in muscle strength. Interestingly, addition of dietary EAAs to the myostatin inhibition with or without resistance exercise training improved muscle quality. Thus, dissection of the underlying mechanisms behind the combined positive effect of dietary EAAs and resistance exercise training on muscle mass and quality can shed light on the discovery of effective therapeutics against muscle wasti...
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This study is consistent with previous evidence showing that inflammaging, or age-related inflammation, is naturally heightened in the nervous system. Moreover, the authors disproved their hypothesis that anti-inflammatory microglia-specific genes are responsible for the elevated inflammatory response in aged brains since the expression of anti-inflammatory mediators was elevated in middle-aged brains following infection. Thus, the cause for the increase in pro-inflammatory genes remains to be elucidated. Mixed Results in Animal Studies of Gene Therapy Targeting Axonal Regrowth https://www.fightaging.org/archiv...
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This study was divided in two phases: CALERIE-1 and CALERIE-2. CALERIE-1 study was performed to assess the possible effects induced by a reduction of 10-30% of caloric intake on body composition parameters and lipid profile after 6 and 12 months in a population of middle-aged non-obese subjects. CALERIE-1 results showed an improvement in lipid and glycemic profile and a reduction in body weight (BW) and fat mass. CALERIE-2 was the largest multi-center study on CRD. A total of 220 subjects were enrolled randomly with a 2:1 allocation into two subgroups: 145 in the CRD group and 75 in the ad libitum group. The CRD gro...
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