scholarly journals Obesity and accelerated epigenetic aging in a high-risk cohort of children

2021 ◽  
Author(s):  
Laura Etzel ◽  
Waylon J. Hastings ◽  
Molly A. Hall ◽  
Christine Heim ◽  
Michael J. Meaney ◽  
...  
Keyword(s):  
High Risk ◽  
Continuous Variable ◽  
Cellular Aging ◽  
Health Study ◽  
Biological Aging ◽  
Blood Leukocytes ◽  
Cell Counts ◽  
Epigenetic Aging ◽  
The Impact ◽  
High Risk Cohort

Background: New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N=273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Results: Higher BMI was significantly correlated with older chronological age, maltreatment status, household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r=0.29, P<.0001), PhenoAge (r=0.25, P<.0001), and DunedinPoAm (r=0.37, P<.0001). In fully adjusted models, GrimAge (b=.06; P=.007) and DunedinPoAm (b=.0017; P<.0001) remained significantly associated with higher BMI. Maltreatment-status was not independently associated with accelerated epigenetic aging after accounting for other factors. Conclusion: In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.

Effect of number of computed tomography (CT) scans during follow-up (FUP) of patients with clinical stage I (CSI) seminoma: A trial-level meta-analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 564-564
Author(s):  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Elena Tagliabue ◽  
Mario Catanzaro ◽  
Davide Biasoni ◽  
...  
Keyword(s):  
High Risk ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Clinical Stage ◽  
Continuous Variable ◽  
Ct Scans ◽  
Occurrence Rate ◽  
Prognostic Effect ◽  
Level Data ◽  
The Impact

564 Background: Despite the overall high cure-rate for patients (pts) with CSI seminoma (sem) regardless of the intervention used, huge discrepancy exists in the number of CT scans that are proposed to pts during FUP period, mainly during active surveillance (AS). The impact of such discrepancy in diagnosing pts with a high-risk relapse was assessed in published literature with a meta-analysis (MA). Methods: We searched for arms of studies of AS or active treatment (AT, adjuvant chemotherapy and radiotherapy) in pts with CSI sem. Meta-analytic techniques were used to pool and compare study level data of AS and AT groups and to study the impact of the number of CT scans (as a continuous variable) during FUP upon the % of pts with CSIII or with IGCCCG intermediate (int) prognosis sem at relapse. Results: 22 studies were analyzed (33 arms, n = 11025 pts). 39.6% had a high-risk sem, 38.8% (n = 4274) underwent AS vs 61.2% (n = 6751) AT. The number of CT scans ≤2y ranged 4-8, and 0-7 for AS and AT groups. Overall, 922 pts experienced a relapse (651 in AS and 271 in AT arms), 73.9% <2y and 22.3% at 2-5y FUP. Statistical modeling showed that the estimated rates of CSIII relapse (6% in AS, 32% in AT group, p = 0.0068) and int prognosis relapse (2% in AS, 11% in AT group, p = 0.0051), were divergent for the two groups. A higher number of CT scans in the first 2 years of FUP tended to reduce the occurrence rate of both endpoints, but failed to reach statistical significance in AS (p = 0.334 for CSIII, unidentifiable for int prognosis relapse), as well as in AT (p = 0.438, p = 0.103). The number of CT scans in 3-5y FUP had an even weaker prognostic effect. Similar trends were observed in AS cohort after adjusting for the CSI risk group. Conclusions: In this trial-level MA we did not find a statistically-significant association between the number of CT scans performed during FUP of CSI sem pts and the diagnosis of high-risk relapses. Huge discrepancy in the total number of CT scans was generally found between arms. In contrast, as expected, the pattern of relapse of CSI sem was different according to the treatment group. Based on these results, there is room for consistently reducing the number of CT scans during FUP of CSI sem pts undergoing AS.

Re(Setting) Epigenetic Clocks: An Important Avenue Whereby Social Conditions Become Biologically Embedded across the Life Course

2021 ◽  
Vol 62 (3) ◽  
pp. 436-453
Author(s):  
Ronald L. Simons ◽  
Man-Kit Lei ◽  
Eric Klopach ◽  
Mark Berg ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Black Women ◽  
Living Arrangements ◽  
Social Conditions ◽  
Health Study ◽  
Biological Aging ◽  
Time To Death ◽  
Epigenetic Aging ◽  
The Social ◽  
The Life Course ◽  
Sociological Studies

Research on biological embedding of the social environment has been expedited by increased availability of biomarkers. Recently, this arsenal of measures has been expanded to include epigenetic clocks that indicate in years the extent to which an individual is older or younger than their chronological age. These measures of biological aging, especially GrimAge, are robust predictors of both illness and time to death. Importantly for sociologists, several studies have linked social conditions to these indices of aging. The present study extends this research using longitudinal data from a sample of 223 black women participating in the Family and Community Health Study. We find that changes in income and living arrangements over an 11-year period predict changes in speed of biological aging. These results provide further support for the idea that epigenetic aging is a mechanism whereby social conditions become biologically embedded. The utility of epigenetic clocks for sociological studies of health are discussed.

scholarly journals Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

2017 ◽  
Vol 135 (2) ◽  
pp. 179-184 ◽  
Author(s):  
Xi Zhang ◽  
Cheng Yang ◽  
Xiangui Peng ◽  
Xinghua Chen ◽  
Yimei Feng
Keyword(s):  
Case Report ◽  
High Risk ◽  
Wilms Tumor ◽  
Combined Treatment ◽  
Promyelocytic Leukemia ◽  
Massive Hemoptysis ◽  
Cell Counts ◽  
Rare Case Report ◽  
High Level ◽  
The Impact

ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1) in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR). To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.

scholarly journals Biological embedding of neighborhood disadvantage and collective efficacy: Influences on chronic illness via accelerated cardiometabolic age

2018 ◽  
Vol 30 (5) ◽  
pp. 1797-1815 ◽  
Author(s):  
Man-Kit Lei ◽  
Steven R. H. Beach ◽  
Ronald L. Simons
Keyword(s):  
Chronic Illness ◽  
Collective Efficacy ◽  
Neighborhood Effects ◽  
Neighborhood Disadvantage ◽  
Integrated Model ◽  
Neighborhood Context ◽  
Health Study ◽  
Biological Aging ◽  
Neighborhood Collective Efficacy ◽  
The Impact

AbstractThe present study extends prior research on the link between neighborhood disadvantage and chronic illness by testing an integrated model in which neighborhood characteristics exert effects on health conditions through accelerated cardiometabolic aging. Hypotheses were tested using a sample of 408 African Americans from the Family and Community Health Study. Using four waves of data spanning young adulthood (ages 18–29), we first found durable effects of neighborhood disadvantage on accelerated cardiometabolic aging and chronic illness. Then, we used marginal structural modeling to adjust for potential neighborhood selection effects. As expected, accelerated cardiometabolic aging was the biopsychosocial mechanism that mediated much of the association between neighborhood disadvantage and chronic illness. This finding provides additional support for the view that neighborhood disadvantage can influence morbidity and mortality by creating social contexts that becomes biologically embedded. Perceived neighborhood collective efficacy served to buffer the relationship between neighborhood disadvantage and biological aging, identifying neighborhood-level resilience factor. Overall, our results indicate that neighborhood context serves as a fundamental cause of weathering and accelerated biological aging. Residing in a disadvantaged neighborhood increases biological wear and tear that ultimately leads to onset of chronic illness, but access to perceived collective efficacy buffers the impact of these neighborhood effects. From an intervention standpoint, identifying such an integrated model may help inform future health-promoting interventions.

scholarly journals Epigenetic age-predictions in mice using pyrosequencing, droplet digital PCR or barcoded bisulfite amplicon sequencing

2020 ◽  
Author(s):  
Yang Han ◽  
Miloš Nikolić ◽  
Michael Gobs ◽  
Julia Franzen ◽  
Gerald de Haan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Model Organism ◽  
Amplicon Sequencing ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Biological Aging ◽  
Epigenetic Aging ◽  
Epigenetic Age ◽  
Trait Locus ◽  
The Impact

AbstractAge-associated DNA methylation reflects aspects of biological aging - therefore epigenetic clocks for mice can help to elucidate the impact of treatments or genetic background on the aging process in this model organism. Initially, age-predictors for mice were trained on genome-wide DNA methylation profiles, whereas we have recently described a targeted assay based on pyrosequencing of DNA methylation at only three CG dinucleotides (CpGs). Here, we have re-evaluated pyrosequencing approaches in comparison to droplet digital PCR (ddPCR) and barcoded bisulfite amplicon sequencing (BBA-seq). At individual CpGs the correlation of DNA methylation with chronological age was slightly higher for pyrosequencing and ddPCR as compared to BBA-seq. On the other hand, BBA-seq revealed that neighboring CpGs tend to be stochastically modified in murine age-associated regions. Furthermore, the binary sequel of methylated and non-methylated CpGs in individual reads can be used for single-read predictions, which may reflect heterogeneity in epigenetic aging. In comparison to C57BL/6 mice the epigenetic age-predictions using BBA-seq were also accelerated in the shorter-lived DBA/2 mice, and in C57BL/6 mice with a lifespan quantitative trait locus of DBA/2 mice. Taken together, we describe further optimized and alternative targeted methods to determine epigenetic clocks in mice.

scholarly journals Predicting cellular aging following exposure to adversity: Does accumulation, recency, or developmental timing of exposure matter?

2018 ◽  
Author(s):  
Sandro Marini ◽  
Kathryn A. Davis ◽  
Thomas W. Soare ◽  
Matthew J. Suderman ◽  
Andrew J. Simpkin ◽  
...  
Keyword(s):  
Middle Childhood ◽  
Repeated Measures ◽  
Selection Procedure ◽  
Cellular Aging ◽  
Sensitive Period ◽  
Developmental Timing ◽  
Biological Aging ◽  
Sensitive Periods ◽  
Epigenetic Aging ◽  
Epigenetic Age

AbstractExposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous health problems, including neuropsychiatric disease. In recent years, measures of DNA methylation-based epigenetic age – known as “epigenetic clocks” – have been used to estimate accelerated epigenetic aging. Yet, few studies have been conducted in children. Using data from the Avon Longitudinal Study of Parents and Children (n=973), we explored the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated the effects of the developmental timing, accumulation, and recency of adversity exposure. We found that exposure to sexual or physical abuse, financial stress, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of the Hannum epigenetic age from the chronological age. Secondary sex-stratified analyses identified particularly strong sensitive period effects, such that by age 7, girls who were exposed to abuse at age 3.5 were biologically older than their unexposed peers by almost 2 months. These effects were undetected in analyses comparing children “exposed” versus “unexposed” to adversity. Our results suggest that exposure to adversity may alter methylation processes in ways that perturb normal cellular aging and that these effects may be heightened during sensitive periods in development. Research is needed to demonstrate the effect of accelerated epigenetic aging on negative health outcomes following childhood adversity exposure.

scholarly journals Neighborhood environment, social cohesion, and epigenetic aging

2020 ◽  
Author(s):  
Chantel L. Martin ◽  
Cavin K. Ward-Caviness ◽  
Radhika Dhingra ◽  
Tarek M. Zikry ◽  
Sandro Galea ◽  
...  
Keyword(s):  
Social Cohesion ◽  
Total Sample ◽  
Neighborhood Environment ◽  
Health Study ◽  
Biological Aging ◽  
Linear Regression Models ◽  
Neighborhood Conditions ◽  
Neighborhood Poverty ◽  
Epigenetic Aging ◽  
Increased Risk

ABSTRACTLiving in adverse neighborhood environments have been linked to increased risk of aging-related diseases and mortality; however, the biological mechanisms explaining this observation remain poorly understood. DNA methylation (DNAm), a proposed biomarker of biological aging responsive to environmental stressors, offers promising insight into molecular pathways. We examined associations of three measures of neighborhood conditions (poverty, quality, and social cohesion) with three different epigenetic clocks (Horvath, Hannum, and Levine) using data from the Detroit Neighborhood Health Study (n=158). Using linear regression models, we evaluated associations in the total sample and stratified by gender and social cohesion. Differential effects by gender were found between men and women. Neighborhood poverty was associated with PhenoAge acceleration among women, but not among men (women: β = 1.4; 95% CI: −0.4, 3.3 vs. men: β = −0.3; 95% CI: −2.2, 1.5) in fully adjusted models. In models stratified on social cohesion, association of neighborhood poverty and quality with accelerated DNAm aging remained elevated for residents living in neighborhoods with lower social cohesion, but were null for those living in neighborhoods with higher social cohesion. Our study suggests that living in adverse neighborhood conditions can speed up epigenetic aging, while positive neighborhood characteristics may buffer effects.

Losing Years Doing Time: Incarceration Exposure and Accelerated Biological Aging among African American Adults

2021 ◽  
pp. 002214652110525
Author(s):  
Mark T. Berg ◽  
Ethan M. Rogers ◽  
Man-Kit Lei ◽  
Ronald L. Simons
Keyword(s):  
African American ◽  
Accelerated Aging ◽  
Premature Mortality ◽  
Health Study ◽  
Biological Aging ◽  
Formerly Incarcerated ◽  
African American Adults ◽  
Epigenetic Aging ◽  
The Family ◽  
Using Data

Research suggests that incarceration exposure increases the prevalence of morbidity and premature mortality. This work is only beginning to examine whether the stressors of the incarceration experience become biologically embedded in ways that affect physiological deterioration. Using data from a longitudinal sample of 410 African American adults in the Family and Community Health Study and an epigenetic index of aging, this study tests the extent to which incarceration accelerates epigenetic aging and whether experiences with violence moderate this association. Results from models that adjust for selection effects suggest that incarceration exposure predicted accelerated aging, leaving formerly incarcerated African American individuals biologically older than their calendar age. Direct experiences with violence also exacerbated the effects of incarceration. These findings suggest that incarceration possibly triggers a stress response that affects a biological signature of physiological deterioration.

scholarly journals Preoperative Troponin Levels and Outcomes of Coronary Surgery Following Myocardial Infarction

2021 ◽  
Author(s):  
Nicholas Hess ◽  
Ibrahim Sultan ◽  
Yisi Wang ◽  
Floyd Thoma ◽  
Arman Kilic
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Artery Bypass ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
Continuous Variable ◽  
High Risk Group ◽  
Lengths Of Stay ◽  
Risk Patients ◽  
The Impact

Background: This study evaluates the impact of peak preoperative troponin level on outcomes of coronary artery bypass grafting (CABG) for non-ST-elevation myocardial infarction (NSTEMI). Methods: This was a retrospective review of patients undergoing isolated CABG from 2011-2018 with presentation of NSTEMI. Patients were stratified into low- and high-risk groups based on median preoperative peak troponin (1.95ng/dL). Major cardiac and cerebrovascular events (MACCE) and mortality were compared. Multivariable analysis was performed to model risk factors for MACCE and mortality. Results: This study included 1,211 patients, 607 low- (≤1.95ng/dL) and 604 high-risk (>1.95ng/dL). Patients were well-matched with respect to age and comorbidity. High-risk patients had lower median preoperative ejection fraction (46.5% [IQR 35.0%-55.0%] vs 53.0% [IQR 40.0%-58.0%]) and higher incidence of preoperative intra-aortic balloon pump (15.9% vs 8.73%). Intensive care unit (47 hours [IQR 26-82] vs 43 hours [IQR 25-69]) and hospital lengths of stay (10 days [IQR 8-13] vs 9 days [IQR 8-12]) were longer in the high-risk group (each P<0.05). Postoperative complications and thirty-day, one- and five-year rates of both MACCE and survival were similar between groups. Peak troponin >1.95ng/dL was not associated with increased hazards for MACCE, mortality, or readmission in multivariable modeling. In sub-analyses, neither increasing troponin as a continuous variable nor peak troponin >10.00ng/mL were associated with increased hazards for these outcomes. Conclusions: Higher preoperative troponin levels are associated with longer lengths of stay but not MACCE or mortality following CABG. Dictating timing of CABG for NSTEMI based on peak troponin does not appear to be warranted.

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