A New Monocyte Epigenetic Clock Reveals Effects of Alcohol Consumption on Epigenetic Aging in Three Independent Cohorts

AbstractBackgroundExcessive alcohol consumption increases the risk of aging-related comorbidities and mortality. Assessing the impact of alcohol consumption on biological age is important for clinical decision-making and prevention. Evidence shows that alcohol alters monocyte function, and age is associated with DNA methylome and transcriptomic changes among monocytes. However, no monocyte-based epigenetic clock is currently available. In this study, we developed a new monocyte-based DNA methylation clock (MonoDNAmAge) by using elastic net regularization. The MonoDNAmAge was validated by benchmarking using epigenetic age acceleration (EAA) in HIV infection. Using MonoDNAmAge clock as well as four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on biological aging in three independent cohorts (N=2,242).ResultsMonoDNAmAge, comprised of 186 CpG sites, was highly correlated with chronological age (rtraining=0.96, p<2.20E-16; rtesting=0.86, p=1.55E-141). The MonoDNAmAge clock predicted an approximately 10-year age acceleration from HIV infection in two cohorts. Quadratic regression analysis showed a nonlinear relationship between MonoDNAmAge and alcohol consumption in the Yale Stress Center Community Study (YSCCS, pmodel=4.55E-08, px2 =7.80E-08) and in the Veteran Aging Cohort Study (VACS, pmodel=1.85E-02, px2 =3.46E-02). MonoDNAmAge and light alcohol consumption showed a negative linear relationship in the Women’s Interagency HIV Study (WIHS, β=-2.63, px=2.82E-06). Heavy consumption increased EAAMonoDNAmAge up to 1.60 years in the VACS while light consumption decreased EAAMonoDNAmAge to 2.66 years in the WIHS. These results were corroborated by the four established epigenetic clocks.ConclusionsWe observed a nonlinear effect of alcohol consumption on epigenetic age that is estimated by a novel monocyte-based “clock” in three distinct cohorts, highlighting the complex effects of alcohol consumption on biological age.

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Exploring Epigenetic Age in Response to Intensive Relaxing Training: A Pilot Study to Slow Down Biological Age

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16173074 ◽

2019 ◽

Vol 16 (17) ◽

pp. 3074 ◽

Cited By ~ 5

Author(s):

Pavanello ◽

Campisi ◽

Tona ◽

Lin ◽

Iliceto

Keyword(s):

Myocardial Infarction ◽

Age Estimation ◽

Healthy Subjects ◽

Molecular Mechanisms ◽

Biological Age ◽

Chronological Age ◽

Biological Aging ◽

Epigenetic Clock ◽

Age Related ◽

Epigenetic Age

DNA methylation (DNAm) is an emerging estimator of biological aging, i.e., the often-defined “epigenetic clock”, with a unique accuracy for chronological age estimation (DNAmAge). In this pilot longitudinal study, we examine the hypothesis that intensive relaxing training of 60 days in patients after myocardial infarction and in healthy subjects may influence leucocyte DNAmAge by turning back the epigenetic clock. Moreover, we compare DNAmAge with another mechanism of biological age, leucocyte telomere length (LTL) and telomerase. DNAmAge is reduced after training in healthy subjects (p = 0.053), but not in patients. LTL is preserved after intervention in healthy subjects, while it continues to decrease in patients (p = 0.051). The conventional negative correlation between LTL and chronological age becomes positive after training in both patients (p < 0.01) and healthy subjects (p < 0.05). In our subjects, DNAmAge is not associated with LTL. Our findings would suggest that intensive relaxing practices influence different aging molecular mechanisms, i.e., DNAmAge and LTL, with a rejuvenating effect. Our study reveals that DNAmAge may represent an accurate tool to measure the effectiveness of lifestyle-based interventions in the prevention of age-related diseases.

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Alcohol consumption and methylation-based measures of biological age

The Journals of Gerontology Series A ◽

10.1093/gerona/glab149 ◽

2021 ◽

Author(s):

Jacob K Kresovich ◽

Alexandra M Martinez Lopez ◽

Emma L Garval ◽

Zongli Xu ◽

Alexandra J White ◽

...

Keyword(s):

Dna Methylation ◽

Alcohol Consumption ◽

Biological Age ◽

Average Lifetime ◽

Epigenetic Clock ◽

Genome Wide ◽

Epigenetic Age ◽

Epigenetic Age Acceleration ◽

The Mean ◽

Average Consumption

Abstract Epigenetic age acceleration is considered a measure of biological aging based on genome-wide patterns of DNA methylation. Although age acceleration has been associated with incidence of diseases and death, less is known about how it is related to lifestyle behaviors. Among 2,316 women, we evaluate associations between self-reported alcohol consumption and various metrics of epigenetic age acceleration. Recent average alcohol consumption was defined as the mean number of drinks consumed per week within the past year; lifetime average consumption was estimated as the mean number of drinks per year drinking. Whole blood genome-wide DNA methylation was measured with HumanMethylation450 BeadChips and used to assess four epigenetic clocks (Hannum, Horvath, PhenoAge, GrimAge) and their corresponding metrics of epigenetic age acceleration (Hannum AgeAccel, Horvath AgeAccel, PhenoAgeAccel, GrimAgeAccel). Although alcohol consumption showed little association with most age acceleration metrics, both lifetime and recent average consumption measures were positively associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β=0.30 years, 95% CI: 0.11, 0.48, p=0.002; recent, per additional 5 drinks/week: β=0.19 years, 95% CI: 0.01, 0.37, p=0.04). In a mutually adjusted model, only average lifetime alcohol consumption remained associated with GrimAgeAccel (lifetime, per additional 135 drinks/year: β=0.27 years, 95% CI: 0.04, 0.50, p=0.02; recent, per 5 additional drinks/week: β=0.05 years, 95% CI: -0.16, 0.26, p=0.64). Although alcohol use does not appear to be strongly associated with biological age measured by most epigenetic clocks, lifetime average consumption is associated with higher biological age assessed by the GrimAge epigenetic clock.

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Religion and Medicine

10.1093/oso/9780190867355.001.0001 ◽

2020 ◽

Author(s):

Jeff Levin ◽

Stephen G. Post

Keyword(s):

Clinical Decision Making ◽

Well Being ◽

Clinical Decision ◽

Religion And Medicine ◽

Physical And Mental Health ◽

Faith Based ◽

Baylor University ◽

Wide Range ◽

History Of ◽

The Impact

In Religion and Medicine, Dr. Jeff Levin, distinguished Baylor University epidemiologist, outlines the longstanding history of multifaceted interconnections between the institutions of religion and medicine. He traces the history of the encounter between these two institutions from antiquity through to the present day, highlighting a myriad of contemporary alliances between the faith-based and medical sectors. Religion and Medicine tells the story of: religious healers and religiously branded hospitals and healthcare institutions; pastoral professionals involved in medical missions, healthcare chaplaincy, and psychological counseling; congregational health promotion and disease prevention programs and global health initiatives; research studies on the impact of religious and spiritual beliefs and practices on physical and mental health, well-being, and healing; programs and centers for medical research and education within major universities and academic institutions; religiously informed bioethics and clinical decision-making; and faith-based health policy initiatives and advocacy for healthcare reform. Religion and Medicine is the first book to cover the full breadth of this subject. It documents religion-medicine alliances across religious traditions, throughout the world, and over the course of history. It summarizes a wide range of material of relevance to historians, medical professionals, pastors and theologians, bioethicists, scientists, public health educators, and policymakers. The product of decades of rigorous and focused research, Dr. Levin has produced the most comprehensive history of these developments and the finest introduction to this emerging field of scholarship.

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Clinical Conundrums When Integrating the QbTest into a Standard ADHD Assessment of Children and Young People

Neuropediatrics ◽

10.1055/s-0040-1722674 ◽

2021 ◽

Author(s):

Carsten Vogt

Keyword(s):

Clinical Practice ◽

Clinical Decision Making ◽

Ecological Validity ◽

Neuropsychological Test ◽

Real Life ◽

Clinical Decision ◽

Hyperactivity Disorder ◽

Standard Clinical Practice ◽

Novel Method ◽

The Impact

AbstractThe uptake of the QbTest in clinical practice is increasing and has recently been supported by research evidence proposing its effectiveness in relation to clinical decision-making. However, the exact underlying process leading to this clinical benefit is currently not well established and requires further clarification. For the clinician, certain challenges arise when adding the QbTest as a novel method to standard clinical practice, such as having the skills required to interpret neuropsychological test information and assess for diagnostically relevant neurocognitive domains that are related to attention-deficit hyperactivity disorder (ADHD), or how neurocognitive domains express themselves within the behavioral classifications of ADHD and how the quantitative measurement of activity in a laboratory setting compares with real-life (ecological validity) situations as well as the impact of comorbidity on test results. This article aims to address these clinical conundrums in aid of developing a consistent approach and future guidelines in clinical practice.

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AAC Assessment and Clinical-Decision Making: The Impact of Experience

Augmentative and Alternative Communication ◽

10.3109/07434618.2012.704521 ◽

2012 ◽

Vol 28 (3) ◽

pp. 148-159 ◽

Cited By ~ 42

Author(s):

Aimee Dietz ◽

Wendy Quach ◽

Shelley K. Lund ◽

Miechelle McKelvey

Keyword(s):

Decision Making ◽

Clinical Decision Making ◽

Clinical Decision ◽

The Impact

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Standardized Synoptic Cancer Pathology Reports — So What and Who Cares?: A Population-Based Satisfaction Survey of 970 Pathologists, Surgeons, and Oncologists

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0656-oa ◽

2013 ◽

Vol 137 (11) ◽

pp. 1599-1602 ◽

Cited By ~ 37

Author(s):

Sara Lankshear ◽

John Srigley ◽

Thomas McGowan ◽

Marta Yurcan ◽

Carol Sawka

Keyword(s):

Decision Making ◽

Clinical Decision Making ◽

Clinical Decision ◽

Physician Satisfaction ◽

Cross Sectional ◽

Cancer Pathology ◽

Report Turnaround Time ◽

Significant Difference ◽

Pathology Reporting ◽

The Impact

Context.—Cancer Care Ontario implemented synoptic pathology reporting across Ontario, impacting the practice of pathologists, surgeons, and medical and radiation oncologists. The benefits of standardized synoptic pathology reporting include enhanced completeness and improved consistency in comparison with narrative reports, with reported challenges including increased workload and report turnaround time. Objective.—To determine the impact of synoptic pathology reporting on physician satisfaction specific to practice and process. Design.—A descriptive, cross-sectional design was utilized involving 970 clinicians across 27 hospitals. An 11-item survey was developed to obtain information regarding timeliness, completeness, clarity, and usability. Open-ended questions were also employed to obtain qualitative comments. Results.—A 51% response rate was obtained, with descriptive statistics reporting that physicians perceive synoptic reports as significantly better than narrative reports. Correlation analysis revealed a moderately strong, positive relationship between respondents' perceptions of overall satisfaction with the level of information provided and perceptions of completeness for clinical decision making (r = 0.750, P < .001) and ease of finding information for clinical decision making (r = 0.663, P < .001). Dependent t tests showed a statistically significant difference in the satisfaction scores of pathologists and oncologists (t169 = 3.044, P = .003). Qualitative comments revealed technology-related issues as the most frequently cited factor impacting timeliness of report completion. Conclusion.—This study provides evidence of strong physician satisfaction with synoptic cancer pathology reporting as a clinical decision support tool in the diagnosis, prognosis, and treatment of cancer patients.

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The Impact of Stressful Life Events on Excessive Alcohol Consumption in the French Population: Findings from the GAZEL Cohort Study

PLoS ONE ◽

10.1371/journal.pone.0087653 ◽

2014 ◽

Vol 9 (1) ◽

pp. e87653 ◽

Cited By ~ 20

Author(s):

Sara L. Tamers ◽

Cassandra Okechukwu ◽

Alex A. Bohl ◽

Alice Guéguen ◽

Marcel Goldberg ◽

...

Keyword(s):

Cohort Study ◽

Alcohol Consumption ◽

Life Events ◽

Stressful Life Events ◽

Stressful Life ◽

French Population ◽

Excessive Alcohol Consumption ◽

Excessive Alcohol ◽

The Impact

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Clinicians’ experiences of using and implementing a medical mobile phone app (QUiPP V2) designed to predict the risk of preterm birth and aid clinical decision making

BMC Medical Informatics and Decision Making ◽

10.1186/s12911-021-01681-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

N. Carlisle ◽

H. A. Watson ◽

J. Carter ◽

K. Kuhrt ◽

P. T. Seed ◽

...

Keyword(s):

Decision Making ◽

Preterm Birth ◽

Cultural Context ◽

Clinical Decision Making ◽

Qualitative Interviews ◽

Scale Up ◽

Clinical Decision ◽

Clinical Trial Registry ◽

Support Tool ◽

The Impact

Abstract Background As the vast majority of women who present in threatened preterm labour (TPTL) will not deliver early, clinicians need to balance the risks of over-medicalising the majority of women, against the potential risk of preterm delivery for those discharged home. The QUiPP app is a free, validated app which can support clinical decision-making as it produces individualised risks of delivery within relevant timeframes. Recent evidence has highlighted that clinicians would welcome a decision-support tool that accurately predicts preterm birth. Methods Qualitative interviews were undertaken as part of the EQUIPTT study (The Evaluation of the QUiPP app for Triage and Transfer) (REC: 17/LO/1802) which aimed to evaluate the impact of the QUiPP app on management of TPTL. Individual semi-structured telephone interviews were used to explore clinicians’ (obstetricians’ and midwives’) experiences of using the QUiPP app and how it was implemented at their hospital sites. Thematic analysis was chosen to explore the meaning of the data, through a framework approach. Results Nineteen participants from 10 hospital sites in England took part. Data analysis revealed three overarching themes which were: ‘experience of using the app’, ‘how QUiPP risk changes practice’ and ‘successfully adopting QUiPP: context is everything’. With these final themes we appeared to have achieved our aim of exploring the clinicians’ experiences of using and implementing the QUiPP app. Conclusion This study explored different clinician’s experiences of implementing the app. The organizational and cultural context at different sites appeared to have a large impact on how well the QUiPP app was implemented. Future work needs to be undertaken to understand how best to embed the intervention within different settings. This will inform scale up of QUiPP app use across the UK and ensure that clinicians have access to this free, easy-to-use tool which can positively aid clinical decision making when caring for women in TPTL. Clinical trial registry and registration number ISRCTN 17846337, registered 08th January 2018, https://doi.org/10.1186/ISRCTN17846337.

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Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging

10.1101/2021.03.11.435028 ◽

2021 ◽

Author(s):

Csaba Kerepesi ◽

Bohan Zhang ◽

Sang-Goo Lee ◽

Alexandre Trapp ◽

Vadim N. Gladyshev

Keyword(s):

Pluripotent Stem Cells ◽

Prenatal Development ◽

Biological Age ◽

Epigenetic Clock ◽

Ground Zero ◽

August Weismann ◽

Age Related ◽

Epigenetic Age ◽

Human Prenatal Development ◽

Changes Over Time

The notion that germline cells do not age goes back to the 19th century ideas of August Weismann. However, being in a metabolically active state, they accumulate damage and other age-related changes over time, i.e., they age. For new life to begin in the same young state, they must be rejuvenated in the offspring. Here, we developed a new multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e. rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (the ground zero) marks the beginning of organismal aging.

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Exploring the role of the Care and Health Information Exchange (CHIE) in clinical decision-making: a realist evaluation

10.1101/2020.08.13.20174276 ◽

2020 ◽

Author(s):

Philip Scott ◽

Elisavet Andrikopoulou ◽

Haythem Nakkas ◽

Paul Roderick

Keyword(s):

Decision Making ◽

Health Information ◽

Information Exchange ◽

Healthcare Professionals ◽

Clinical Decision Making ◽

Social Care ◽

Health Information Exchange ◽

Clinical Decision ◽

Health And Social Care ◽

The Impact

Background: The overall evidence for the impact of electronic information systems on cost, quality and safety of healthcare remains contested. Whilst it seems intuitively obvious that having more data about a patient will improve care, the mechanisms by which information availability is translated into better decision-making are not well understood. Furthermore, there is the risk of data overload creating a negative outcome. There are situations where a key information summary can be more useful than a rich record. The Care and Health Information Exchange (CHIE) is a shared electronic health record for Hampshire and the Isle of Wight that combines key information from hospital, general practice, community care and social services. Its purpose is to provide clinical and care professionals with complete, accurate and up-to-date information when caring for patients. CHIE is used by GP out-of-hours services, acute hospital doctors, ambulance service, GPs and others in caring for patients. Research questions: The fundamental question was How does awareness of CHIE or usage of CHIE affect clinical decision-making? The secondary questions were What are the latent benefits of CHIE in frontline NHS operations? and What is the potential of CHIE to have an impact on major NHS cost pressures? The NHS funders decided to focus on acute medical inpatient admissions as the initial scope, given the high costs associated with hospital stays and the patient complexities (and therefore information requirements) often associated with unscheduled admissions. Methods: Semi-structured interviews with healthcare professionals to explore their experience about the utility of CHIE in their clinical scenario, whether and how it has affected their decision-making practices and the barriers and facilitators for their use of CHIE. The Framework Method was used for qualitative analysis, supported by the software tool Atlas.ti. Results: 21 healthcare professionals were interviewed. Three main functions were identified as useful: extensive medication prescribing history, information sharing between primary, secondary and social care and access to laboratory test results. We inferred two positive cognitive mechanisms: knowledge confidence and collaboration assurance, and three negative ones: consent anxiety, search anxiety and data mistrust. Conclusions: CHIE gives clinicians the bigger picture to understand the patient's health and social care history and circumstances so as to make confident and informed decisions. CHIE is very beneficial for medicines reconciliation on admission, especially for patients that are unable to speak or act for themselves or who cannot remember their precise medication or allergies. We found no clear evidence that CHIE has a significant impact on admission or discharge decisions. We propose the use of recommender systems to help clinicians navigate such large volumes of patient data, which will only grow as additional data is collected.

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