Biological Psychiatry, Journal Year: 2023, Volume and Issue: 93(4), P. 296 - 297
Published: Jan. 16, 2023
Language: Английский
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: April 19, 2023
Biological aging is accompanied by increasing morbidity, mortality, and healthcare costs; however, its molecular mechanisms are poorly understood. Here, we use multi-omic methods to integrate genomic, transcriptomic, metabolomic data identify biological associations with four measures of epigenetic age acceleration a human longevity phenotype comprising healthspan, lifespan, exceptional (multivariate longevity). Using transcriptomic imputation, fine-mapping, conditional analysis, 22 high confidence seven multivariate longevity. FLOT1, KPNA4, TMX2 novel, genes associated acceleration. In parallel, cis-instrument Mendelian randomization the druggable genome associates TPMT NHLRC1 aging, supporting imputation findings. Metabolomics identifies negative effect non-high-density lipoprotein cholesterol lipoproteins on longevity, but not Finally, cell-type enrichment analysis implicates immune cells precursors in and, more modestly, Follow-up cell traits suggests lymphocyte subpopulations lymphocytic surface molecules affect Our results highlight targets pathways involved facilitate comparisons clocks
Language: Английский
Citations
24
Alcohol Clinical and Experimental Research, Journal Year: 2024, Volume and Issue: 48(2), P. 250 - 259
Published: Jan. 26, 2024
Abstract Background Alcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation gene expression neuroinflammation‐related pathways the brain, aging represents a potentially important construct understanding adverse effects substance disorders. Epigenetic clocks have shown blood samples from individuals AUD. However, no systematic evaluation age measures across different tissues brain regions has been undertaken. Methods markers (BioAge markers), we assessed Levine's Horvath's epigenetic clocks, telomere length (DNAmTL), (TL), mitochondrial copy number (mtDNAcn) postmortem Brodmann Area 9 (BA9), caudate nucleus, ventral striatum ( N = 63–94), whole 179) without To evaluate association between status BioAge markers, performed linear regression analyses while adjusting covariates. Results The majority were significantly chronological all samples. clock DNAmTL indicative BA9 samples, showed opposite effect BA9. No significant TL mtDNAcn was detected. Measured only small correlations none brain. Conclusions present study first to simultaneously investigate length, We found evidence measured clock, DNAmTL. Additional same are needed draw valid conclusions about congruence
Language: Английский
Citations
7
Biological Psychiatry, Journal Year: 2023, Volume and Issue: 94(9), P. 694 - 705
Published: Feb. 9, 2023
Language: Английский
Citations
15
Biological Psychiatry, Journal Year: 2023, Volume and Issue: 95(3), P. 245 - 255
Published: Sept. 9, 2023
Language: Английский
Citations
15
Alcohol Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: unknown
Published: March 28, 2025
Abstract Background Chronic heavy alcohol use is a major risk factor for premature aging and age‐related diseases. DNA methylation (DNAm)‐based epigenetic clocks are novel tools predicting biological age. However, the newest configurations, causality‐enriched clocks, have not been assessed in context of consumption disorder (AUD). Methods Epigenetic was evaluated sample 615 individuals (372 AUD patients 243 healthy controls) by applying GrimAge Version 1 (V1) 2 (V2) alongside three (CausAge, DamAge, AdaptAge). A linear model controlling diagnosis, sex, race, BMI, smoking status, five blood cell types leveraged to test associations between alcohol‐related metrics age‐adjusted clocks. Results V1 V2 maintained significant with drinking behavior measures within total both young (<40 years old) old (≥40 subgroups. Generally, slightly outperformed V1, while none demonstrated AUD. subgroup, DamAge had association number drinks. Across age subgroups, liver function enzymes, consistently sustained stronger compared V1. Among fourth‐generation exhibited gamma‐glutamyl transferase (GGT) aspartate aminotransferase subgroup; CausAge displayed GGT sample. Examining clinical biomarkers, showed improved C‐reactive protein Conclusions Overall, we observed moderately performance majority parameters tested. The lacked but demonstrate complexities inspire further research dynamics.
Language: Английский
Citations
0
Oxford University Press eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 271 - 290
Published: Feb. 20, 2025
Abstract Translational Geroscience is rooted in the geroscience paradigm which seeks to define genetic, molecular, and cellular mechanisms that make age major risk factor driver of most chronic conditions diseases older people. The final aim convert this fundamental knowledge into effective interventions promote healthy ageing. In chapter, we discuss how interfaces with life course epidemiology through emerging tools assess biological age. It has potential shift focus medicine from current model disease treatment an emphasis on counteracting ageing phenotypes during one’s full expand health expectancy. We claim advances biomarker technologies, science approaches, mechanism-based therapeutic strategies, a day when individuals will be spending their good within sight.
Language: Английский
Citations
0
Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(5), P. 525 - 561
Published: March 30, 2024
Language: Английский
Citations
3
Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111365 - 111365
Published: April 1, 2025
The endocannabinoid system is involved in multiple drug-related behaviors and the transient increase endogenous cannabinoids endocannabinoid-like molecules contributes to healthy adaptation stress exposure. Oleoylethanolamide (OEA) belongs N-acylethanolamines interacts with system. In this study, we investigated effect of systemic OEA treatment (10 mg/kg), before or after social defeat (SD), on ethanol self-administration (SA). Mice were divided into non-stressed (EXP) stressed (SD) groups randomly assigned a condition (control-CTRL, 10OEA). EXP/SD-OEA group mice received four doses each SD encounter, while EXP/SD-10OEA daily dose for 10 consecutive days following Three weeks SD, trained self-administer 20 % (vol/vol) solution. Upon extinction, cue-induced reinstatement test was performed. Our results showed that both treatments effectively prevented stress-induced consumption observed defeated mice. No significant effects relapse-like behavior observed. Additionally, found animals exposed during encounters reduced nuclear factor kappa B (NF-κB) levels, suggesting an anti-inflammatory OEA, tumor necrosis (TNFα) gene expression decreased animals. summary, these findings suggest exogenously increasing levels counteracts adverse drinking having some impact inflammatory patterns.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: April 29, 2025
Abstract Reactive microglia are associated with multiple brain diseases that may have specific disease phenotypes. Studies of human cortical in alcohol use disorder (AUD) characterized reactive microglial subtypes by transcriptome or histology. Preclinical studies found proinflammatory signaling and contribute to increases drinking preference, behaviors unique AUD. This study post-mortem AUD combines immunoreactivity (+IR) protein changes gene expression (mRNA) orbital frontal cortex (OFC) an effort better characterize the Since linked astrocytes (GFAP+IR), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine (8-OHdG+IR), neurodegeneration (NeuN, MAP2+IR), we assessed these markers within OFC. were identified Iba1, CD11b (Mac1-OX42), CX3CR1, CSF1R, CD68, CCR2, P2RY12, SYK, TFE3+IR OFC compared control moderate drinkers. Tmem119+IR was decreased brain. Several genes had parallel +IR mRNA. However, several commonly used identify did not show mRNA, including CSF1R+IR. Overall, monocyte phagocytic markers, but TREM2, DAP, complement genes. highly correlated astrocyte GFAP+IR, stress 8-OHdG+IR, loss neurons MAP2+IR). Mediation analysis indicated both stress, only significantly (NeuN+IR). These findings supported mouse finding chronic ethanol exposure is inhibited DREADD blockade activation. Our support a distinct phenotype activates astrocytes, contributing possibly heavy drinking.
Language: Английский
Citations
0
Journal of Mood and Anxiety Disorders, Journal Year: 2023, Volume and Issue: 3, P. 100026 - 100026
Published: Sept. 21, 2023
Advanced epigenetic age is associated with psychopathology and may help to explain the link between physical health morbidity mortality. Using a longitudinal sample of 171 trauma-exposed Veterans, we modeled rate change in across two time points (averaging 5.58 years apart) using algorithms (GrimAge Horvath) tested associations posttraumatic stress disorder (PTSD), alcohol use (AUD), depression. Results showed that PTSD (β = .199) AUD .186) were quickened
Language: Английский
Citations
4