scholarly journals Shift work, DNA methylation and epigenetic age

2019 ◽  
Vol 48 (5) ◽  
pp. 1536-1544 ◽  
Author(s):  
Alexandra J White ◽  
Jacob K Kresovich ◽  
Zongli Xu ◽  
Dale P Sandler ◽  
Jack A Taylor

Abstract Background Shift work has been associated with increased risk of age-related morbidity and mortality. Biological age, estimated using DNA methylation (DNAm), may quantify the biological consequences of shift work on the risk of age-related disease. We examined whether prior employment in shift-working occupations was associated with epigenetic age acceleration. Methods In a sample of non-Hispanic White women aged 35–74 (n = 2574), we measured DNAm using the Illumina Infinium Human450 BeadChip and calculated DNAm age using three established epigenetic clocks. Age-acceleration metrics were derived by regressing DNAm age on chronological age and predicting the residuals. Using linear regression, we estimated associations between shift work history and age acceleration. We also conducted an epigenome-wide association study using robust linear-regression models corrected with false discovery rate (FDR) q-values. Results Approximately 7% of women reported any shift work. Higher age acceleration was observed for a 1-year increase in overall [β = 0.11, 95% confidence interval (CI): 0.02–0.21] and night-specific shift work (β = 0.12, 95% CI: 0.03–0.21). The association was strongest for ≥10 years of night shift work (β = 3.16, 95% CI: 1.17–5.15). From the epigenome-wide association study, years of overall and night shift work were associated with DNAm at 66 and 85 CpG sites (FDR < 0.05), respectively. Years of night shift work was associated with lower methylation of a CpG in the gene body of ZFHX3 (cg04994202, q = 0.04), a gene related to circadian rhythm. Conclusions Shift work was associated with differential CpG site methylation and with differential DNAm patterns, measured by epigenetic age acceleration, consistent with long-term negative health effects.

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Sadiya S Khan ◽  
Yinan Zheng ◽  
Laura A Colangelo ◽  
Wei Zhang ◽  
Cora E Lewis ◽  
...  

Background: Obesity is associated with increased risk of cardiovascular and other age-related diseases that may represent accelerated aging. As methylation levels in DNA change with aging, epigenetic age (EA), which integrates whole-genome methylation has emerged as a novel biomarker of aging and has been associated with mortality and age-related morbidity. Epigenetic age acceleration (EAA), is based on the residual value of 353 previously defined methylation markers regressed on chronologic age (CA), and is thus independent of CA. Therefore, we sought to examine the association of obesity and EAA in midlife. Methods: A subset of participants in the CARDIA cohort (n=1200) randomly selected (balanced on race and sex) underwent genome-wide DNA methylation profiling with the Illumina EPIC array from exam year 15 (2000-01 [age 33-45 years]) and 20 (2005-06 [38-50 years] for calculation of EAA. Body mass index (BMI) was measured at Y15 and Y20, respectively. We used linear regression to examine the association of obesity (independent variable) with EAA after adjusting for CA, race, sex, education, study center, smoking status, physical activity, and alcohol intake. Results: Participants were 52% female and 41% black and had mean BMI 28.5±6.2 kg/m 2 at Y15 and 29.2±6.4 kg/m 2 at Y20. At Y15, participants who were obese had 1.04 (0.38) years higher EAA compared to normal BMI participants (p<0.01, Figure) . Similar results were observed at Y20. Results were similar when evaluating the association of BMI continuously with EAA (p<0.05). Conclusions: EAA is a promising molecular biomarker of aging associated with obesity. Changes in DNA methylation may serve as an intermediate phenotype prior to the onset of age-associated pathologies related to obesity.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15600-e15600
Author(s):  
Chenyu Sun ◽  
Ce Cheng ◽  
Kelly Kozma ◽  
Gopika Chandra ◽  
Na Hyun Kim ◽  
...  

e15600 Background: Globally, more than 1.8 million people were diagnosed of colorectal cancer (CRC) in 2018, with over 30% of CRC in the rectum. Shift-work, involving circadian disruption, sleep deprivation and lifestyle changes, was designated as a probable cause of cancer by The International Agency for Research on Cancer. Previous studies investigating the impact of permanent night-shift work and rotating shift-work on rectal cancer risk showed controversial results. Thus, this meta-analysis was conducted. Methods: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to January 2021 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the shift-work and rectal cancer risk. Based on heterogeneity significance, random-effect or fixed-effect model was used. Subgroup analyses were conducted to explore the night-shift and rotating-shift, respectively. Sensitivity analysis and publication bias detection were performed, and trim and fill analysis was also conducted. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 15.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Results: Thirty-seven articles were obtained from database searching. Three articles involving 1,063 rectal cancer cases were included. All studies were considered moderate to high quality. All included studies investigated on the association between shift-work and rectal cancer risk. A statistically significant association between shift-work and increased rectal cancer risk was found (OR 1.53, 95%CI: 1.31, 1.79, P< 0.00001, I 2 = 35%). In subgroup analyses, night-shift work was associated with a non-statistically significant increased risk of rectal cancer (OR 1.25, 95%CI: 0.47, 3.32, P = 0.66, I 2 = 93%). In contrast, Rotating-shift was associated with a statistically significant increased rectal cancer risk (OR 1.35, 95%CI: 1.10, 1.65, P = 0.004, I 2 = 6%). Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test (t = 1.69, P = 0.341), and Begg's test (z = 1.04, P = 0.296) found no publication bias of analysis. Trim and fill analysis on fixed-effect model showed the pooled OR kept stable after adding two “missing” studies (OR 1.403, 95%CI: 1.224, 1.609, P <0.05). Conclusions: The current meta-analysis demonstrates that shift-work is associated with increased rectal cancer risk. However, no association between night-shift work and rectal cancer risk was found. In contrast, association between rotating-shift work and increased rectal cancer risk was found. More original studies on this topic are needed to further explore shift-work impacts on rectal cancer risk.


2021 ◽  
Vol 13 ◽  
Author(s):  
Pei-Lun Kuo ◽  
Ann Zenobia Moore ◽  
Frank R. Lin ◽  
Luigi Ferrucci

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.


2021 ◽  
Vol 4 (1) ◽  
pp. 30
Author(s):  
Sri Ratna Dwiningsih ◽  
Samsulhadi Samsulhadi ◽  
Arif Tunjungseto ◽  
Monika Lijuwardi ◽  
Arsana Wiyasa

Introduction: Earlier menopause has been associated with increased risk of cardiovascular disease, osteoporosis, shorter life expectancy and even cognitive decline. There are many factors that cause differences in the age of menopause in women, one of these environmental factors is a history of night shift work as a consequence of a job. It is not yet known whether female medical workers, with a history of night shifts, get earlier menopause.Methods: This case control study was conducted among 57 female night workers of the Dr. Soetomo General Academic Hospital. Data collection was conducted from December 2019 - March 2020. The study sample was postmenopausal health workers (nurse and midwife) and administrators. The instrument used in this study was a list of interview questions. The data was processed using SPSS software release 23.Results: The results show that from 45 children diagnosed with ALL, 53% are of the age ≤ 5 years old, with 58% males and 42% females. 13% of the patients are in the high risk group and 87% are in the standard risk group. Nutritional statuses of patients are 2% of them obese experienced remission after induction phase therapy, 56% normal with 80% of them experienced remission. 40% underweight with 89% of them experienced remission and 11% not experienced remission, 2% malnutrition and experienced remission. There is no correlation between the nutritional status of children with acute lymphoblastic leukemia with the outcome of induction phase (p = 0.798).Conclusion: In conclusion, there is no correlation between nutritional status and remission outcome of patients with ALL in the induction phase of therapy. However, high percentage of underweight patients shows nutrition needs special attention to improve therapy outcomes. 


Epigenomics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1429-1439 ◽  
Author(s):  
Eleftheria Theodoropoulou ◽  
Lars Alfredsson ◽  
Fredrik Piehl ◽  
Francesco Marabita ◽  
Maja Jagodic

Aim: Accumulating evidence links epigenetic age to diseases and age-related conditions, but little is known about its association with multiple sclerosis (MS). Materials & methods: We estimated epigenetic age acceleration measures using DNA methylation from blood or sorted cells of MS patients and controls. Results: In blood, sex (p = 4.39E-05) and MS (p = 2.99E-03) explained the variation in age acceleration, and isolated blood cell types showed different epigenetic age. Intrinsic epigenetic age acceleration and extrinsic epigenetic age acceleration were only associated with sex (p = 2.52E-03 and p = 1.58E-04, respectively), while PhenoAge Acceleration displayed positive association with MS (p = 3.40E-02). Conclusion: Different age acceleration measures are distinctly influenced by phenotypic factors, and they might measure separate pathophysiological aspects of MS. Data deposition: DNA methylation data can be accessed at Gene Expression Omnibus database under accession number GSE35069, GSE43976, GSE106648, GSE130029, GSE130030.


Author(s):  
Maja Popovic ◽  
Valentina Fiano ◽  
Elena Isaevska ◽  
Chiara Moccia ◽  
Morena Trevisan ◽  
...  

Abstract Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7–17) months were used to estimate Horvath’s DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: −0.79 to 2.34 for low/medium education; 0.96, 95% CI: −1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath’s method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 190-190
Author(s):  
Chenyu Sun ◽  
Ce Cheng

190 Background: Globally, more than 570,000 people are diagnosed of esophageal cancer each year. Shift-work involving circadian disruption was designated as a probable cause of cancer by The International Agency for Research on Cancer. Previous studies investigating the relationship between shift-work and esophageal cancer among showed controversial results. Thus, this meta-analysis was conducted. Methods: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to September 2020 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds risk (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the shift-work and esophageal cancer risk. Random-effect or fixed-effect model was used to calculate the pooled OR, based on heterogeneity significance. Subgroup analyses were conducted based on night-shift versus rotating-shift. Sensitivity analysis and publication bias detection were also performed. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 12.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Results: 21 articles were obtained from database searching, and 9 articles were obtained from other sources. 3 articles involving 52,098 participants were included. All studies were considered moderate to high quality. All included studies investigated only males on the association between shift-work and esophageal cancer risk. A statistically significant association between shift-work and increased esophageal cancer risk among males was found (OR 2.09, 95%CI: 1.48, 2.94, P< 0.0001, I 2= 29%). In subgroup analyses, night-shift work was associated with a non-statistically significant increased risk of esophageal cancer (OR 1.56, 95%CI: 0.96, 2.53, P= 0.07, I 2= 0%). In contrast, Rotating-shift was associated with increased esophageal cancer risk (OR 2.80, 95%CI: 1.72, 4.57, P < 0.0001, I 2= 0%). Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test, and Begg's test found no publication bias of analysis (P = 0.572). Conclusions: The current meta-analysis demonstrates that shift-work is associated with increased esophageal cancer risk for males. However, no association between night-shift work and esophageal cancer risk was found. In contrast, association between rotating-shift work and increased esophageal cancer risk was found. Original studies on females regarding shift-work and esophageal cancer risk are lacking. More original studies on this topic for both male and female are needed to further explore shift-work impacts on esophageal cancer risk.


2019 ◽  
Vol 76 (10) ◽  
pp. 733-738 ◽  
Author(s):  
Kyriaki Papantoniou ◽  
Jennifer Massa ◽  
Elizabeth Devore ◽  
Kassandra L Munger ◽  
Tanuja Chitnis ◽  
...  

ObjectivesNight shift work has been suggested as a possible risk factor for multiple sclerosis (MS). The objective of the present analysis was to prospectively evaluate the association of rotating night shift work history and MS risk in two female cohorts, the Nurses’ Health Study (NHS) and NHSII.MethodsA total of 83 992 (NHS) and 114 427 (NHSII) women were included in this analysis. We documented 579 (109 in NHS and 470 in NHSII) incident physician-confirmed MS cases (moderate and definite diagnosis), including 407 definite MS cases. The history (cumulative years) of rotating night shifts (≥3 nights/month) was assessed at baseline and updated throughout follow-up. Cox proportional hazards models were used to estimate HRs and 95% CIs for the association between rotating night shift work and MS risk adjusting for potential confounders.ResultsWe observed no association between history of rotating night shift work and MS risk in NHS (1–9 years: HR 1.03, 95% CI 0.69 to 1.54; 10+ years: 1.15, 0.62 to 2.15) and NHSII (1–9 years: HR 0.90, 95% CI 0.74 to 1.09; 10+ years: 1.03, 0.72 to 1.49). In NHSII, rotating night shift work history of 20+ years was significantly associated with MS risk, when restricting to definite MS cases (1–9 years: HR 0.88, 95% CI 0.70 to 1.11; 10–19 years: 0.98, 0.62 to 1.55; 20+ years: 2.62, 1.06 to 6.46).ConclusionsOverall, we found no association between rotating night shift work history and MS risk in these two large cohorts of nurses. In NHSII, shift work history of 20 or more years was associated with an increased risk of definite MS diagnosis.


2016 ◽  
Vol 32 (1) ◽  
pp. 48-63 ◽  
Author(s):  
Janne Grønli ◽  
Peter Meerlo ◽  
Torhild T. Pedersen ◽  
Ståle Pallesen ◽  
Silje Skrede ◽  
...  

Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistribution of sleep to the endogenous active phase. Rest-work also led to higher electroencephalogram (EEG) slow-wave (1-4 Hz) energy in quiet wakefulness during work-sessions, suggesting a degraded waking state. After the daily work-sessions, being in their endogenous active phase, rest-workers slept less and had higher gamma (80-90 Hz) activity during wake than active-workers. Finally, rest-work induced an enduring shift in the main sleep period and attenuated the accumulation of slow-wave energy during NREM sleep. A comparison of recovery data from 12:12 LD and constant dark conditions suggests that reduced time in NREM sleep throughout the recorded 7-day recovery phase induced by rest-work may be modulated by circadian factors. Our data in rats show that enforced night-work-like activity during the normal resting phase has pronounced acute and persistent effects on sleep and waking behavior. The study also underscores the potential importance of animal models for future studies on the health consequences of night-shift work and the mechanisms underlying increased risk for diseases.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Ayu Munawaroh

Within the last decade, shift work has been an important issue, because it can give negative impacts to the worker’s body. International Agency for Research on Cancer (IARC) on 2007 had classified the shift work which disturb circadian rhythm as probably carcinogenic. One of the cancer which often been researched is breast cancer. Moreover, Around 572% of female workers are in professional and service sector that closely related to night shift work. This evidence based case report aims to know the relation between night shift work and breast cancer in female workers. Based on electronic database literature searching on September 26th 2018 using PubMed, EBSCo (MEDLINE with fulltext), and ProQuest, there are seven meta-analysis which useful to be critically appraised. The result of critical appraisal was increased risk of breast cancer in night shift female workers. Therefore, there was a sufficient validity with number needed to harm by 15 people. It can be concluded that night shift work, with duration and certain period could be risk factor for breast cancer in female workers, then further approaches are needed regarding this matter.


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