Marijuana use and DNA methylation-based biological age in young adults

BACKGROUND: Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana\u27s effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation. RESULTS: A random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with available whole blood at examination years (Y) 15 and Y20 underwent epigenomic profiling. Four EAA estimates (intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration) were calculated from DNA methylation levels measured at Y15 and Y20. Ever use and cumulative marijuana-years were calculated from the baseline visit to Y15 and Y20, and recent marijuana use (both any and number of days of use in the last 30 days) were calculated at Y15 and Y20. Ever use of marijuana and each additional marijuana-year were associated with a 6-month (P \u3c 0.001) and a 2.5-month (P \u3c 0.001) higher average in GrimAge acceleration (GAA) using generalized estimating equations, respectively. Recent use and each additional day of recent use were associated with a 20-month (P \u3c 0.001) and a 1-month (P \u3c 0.001) higher GAA, respectively. A statistical interaction between marijuana-years and alcohol consumption on GAA was observed (P = 0.011), with nondrinkers exhibiting a higher GAA (β = 0.21 [95% CI 0.05, 0.36], P = 0.008) compared to heavy drinkers (β = 0.05 [95% CI - 0.09, 0.18], P = 0.500) per each additional marijuana-year. No associations were observed for the remaining EAA estimates. CONCLUSIONS: These findings suggest cumulative and recent marijuana use are associated with age-related epigenetic changes that are related to lifespan. These observed associations may be modified by alcohol consumption. Given the increase in use and legalization, these findings provide novel insight on the effect of marijuana use on the aging process as captured through blood DNA methylation

Coffee and tea consumption in the early adult lifespan and left ventricular function in middle age: the CARDIA study

AIMS: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. METHODS AND RESULTS: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010-2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e )]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985-1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of \u3c 1, 1-2, 3-4, and \u3e 4 cups/day with non-coffee drinkers were beta = -0.30%, P \u3c 0.05; beta = -0.35%, P \u3c 0.05; beta = -0.32%, P \u3c 0.05; beta = -0.40%, P \u3e 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e , beta coefficients when comparing coffee drinkers of \u3c 1, 1-2, 3-4, and \u3e 4 cups/day with non-coffee drinkers were beta = -0.29, P \u3c 0.05; beta = -0.38, P \u3c 0.01; beta = -0.20, P \u3e .05; and beta = -0.37, P \u3e 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption ( \u3e 4 cups/day) was associated with worse LVEF (beta = -1.69, P \u3c 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P \u3e 0.05 for all). CONCLUSIONS: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption ( \u3e 4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function

Association of smoking and right ventricular function in middle age: CARDIA study

Objective: To evaluate the association of cigarette smoking and right ventricular (RV) systolic and diastolic functions in a population-based cohort of individuals at middle age. Methods: This cross-sectional study included participants who answered the smoking questionnaire and underwent echocardiography at the Coronary Artery Risk Development in Young Adulthood year 25 examination. RV systolic function was assessed by echocardiographic-derived tricuspid annular plane systolic excursion (TAPSE) and by right ventricular peak systolic velocity (RVS\u27), while RV diastolic function was evaluated by early right ventricular tissue velocity (RVE\u27). Multivariable linear regression models assessed the relationship of smoking with RV function, adjusting for age, sex, race, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, diabetes mellitus, alcohol consumption, pulmonary function, left ventricular systolic and diastolic function and coronary artery calcium score. Results: A total of 3424 participants were included. The mean age was 50+/-4 years; 57% were female; and 53% were black. There were 2106 (61%) never smokers, 750 (22%) former smokers and 589 (17%) current smokers. In the multivariable analysis, current smokers had significantly lower TAPSE (beta=-0.082, SE=0.031, p=0.008), RVS\u27 (beta=-0.343, SE=0.156, p=0.028) and RVE\u27 (beta=-0.715, SE=0.195, p \u3c 0.001) compared with never smokers. Former smokers had a significantly lower RVE\u27 compared with never smokers (beta=-0.414, SE=0.162, p=0.011), whereas no significant difference in RV systolic function was found between former smokers and never smokers. Conclusions: In a large multicenter community-based biracial cohort of middle-aged individuals, smoking was independently related to both worse RV systolic and diastolic functions

CNS Expression of B7-H1 Regulates Pro-Inflammatory Cytokine Production and Alters Severity of Theiler's Virus-Induced Demyelinating Disease

The CNS is a unique organ due to its limited capacity for immune surveillance. As macrophages of the CNS, microglia represent a population originally known for the ability to assist neuronal stability, are now appreciated for their role in initiating and regulating immune responses in the brain. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a mouse model of multiple sclerosis (MS). In response to TMEV infection in vitro, microglia produce high levels of inflammatory cytokines and chemokines, and are efficient antigen-presenting cells (APCs) for activating CD4+ T cells. However, the regulatory function of microglia and other CNS-infiltrating APCs in response to TMEV in vivo remains unclear. Here we demonstrate that microglia increase expression of proliferating cell nuclear antigen (PCNA), and phenotypically express high levels of major histocompatibility complex (MHC)-Class I and II in response to acute infection with TMEV in SJL/J mice. Microglia increase expression of the inhibitory co-stimulatory molecule, B7-H1 as early as day 5 post-infection, while CNS-infiltrating CD11b+CD11c−CD45HIGH monocytes/macrophages and CD11b+CD11c+CD45HIGH dendritic cells upregulate expression of B7-H1 by day 3 post-infection. Utilizing a neutralizing antibody, we demonstrate that B7-H1 negatively regulates TMEV-specific ex vivo production of interferon (IFN)-γ, interleukin (IL)-17, IL-10, and IL-2 from CD4+ and CD8+ T cells. In vivo blockade of B7-H1 in SJL/J mice significantly exacerbates clinical disease symptoms during the chronic autoimmune stage of TMEV-IDD, but only has minimal effects on viral clearance. Collectively, these results suggest that CNS expression of B7-H1 regulates activation of TMEV-specific T cells, which affects protection against TMEV-IDD

Reconstructing Speech from Human Auditory Cortex

Direct brain recordings from neurosurgical patients listening to speech reveal that the acoustic speech signals can be reconstructed from neural activity in auditory cortex

Exome chip analysis identifies low-frequency and rare variants in MRPL38 for white matter hyperintensities on brain MRI

International audienc

The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles

Search for New Physics in Electronic Recoil Data from XENONnT

We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3)  events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter

Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = -0.59, p-value = 3.14 × 10-6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology