scholarly journals BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI

2021 ◽  
Author(s):  
Sara Lundgren ◽  
Sara Kuitunen ◽  
Kirsi H. Pietiläinen ◽  
Mikko Hurme ◽  
Mika Kähönen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Meta Analysis ◽  
Accelerated Aging ◽  
Positive Association ◽  
Shared Environment ◽  
Epigenetic Clock ◽  
450K Array ◽  
Cross Sectional ◽  
Age Related ◽  
Epigenetic Age

ABSTRACTBackgroundObesity is a heritable complex phenotype which can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various “epigenetic clocks.” Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely relates with mortality.ObjectivesWe aimed to assess the cross-sectional association of BMI with age acceleration in twins to limit confounding by genetics and shared environment.Methods and ResultsParticipants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twins, and DNAm was measured using the Illumina 450k array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 × 10−12) per 1-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (ΔBMI > 3 kg/m2) had an epigenetic age 5.2 months older than their lighter co-twin (p-value = 0.0074). We also found a positive association between log(HOMA-IR) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 0.0025) from adjusted models.ConclusionWe identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.

scholarly journals Epigenetic Clocks and Allostatic Load Reveal Potential Sex-Specific Drivers of Biological Aging

2019 ◽  
Author(s):  
Cathal McCrory ◽  
Giovanni Fiorito ◽  
Sinead McLoughlin ◽  
Silvia Polidoro ◽  
Cliona Ni Cheallaigh ◽  
...  
Keyword(s):  
Allostatic Load ◽  
Accelerated Aging ◽  
Community Dwelling ◽  
Biological Aging ◽  
Cross Sectional ◽  
Metabolic Dysregulation ◽  
Age Related ◽  
Epigenetic Age ◽  
Epigenetic Age Acceleration ◽  
Dna Methylation Age

Abstract Allostatic load (AL) and epigenetic clocks both attempt to characterize the accelerated aging of biological systems, but at present it is unclear whether these measures are complementary or distinct. This study examines the cross-sectional association of AL with epigenetic age acceleration (EAA) in a subsample of 490 community-dwelling older adults participating in The Irish Longitudinal study on Aging (TILDA). A battery of 14 biomarkers representing the activity of four different physiological systems: immunological, cardiovascular, metabolic, renal, was used to construct the AL score. DNA methylation age was computed according to the algorithms described by Horvath, Hannum, and Levine allowing for estimation of whether an individual is experiencing accelerated or decelerated aging. Horvath, Hannum, and Levine EAA correlated 0.05, 0.03, and 0.21 with AL, respectively. Disaggregation by sex revealed that AL was more strongly associated with EAA in men compared with women as assessed using Horvath’s clock. Metabolic dysregulation was a strong driver of EAA in men as assessed using Horvath and Levine’s clock, while metabolic and cardiovascular dysregulation were associated with EAA in women using Levine’s clock. Results indicate that AL and the epigenetic clocks are measuring different age-related variance and implicate sex-specific drivers of biological aging.

Meta-analysis of the age-associated decline in maximal aerobic capacity in men: relation to training status

2000 ◽  
Vol 278 (3) ◽  
pp. H829-H834 ◽  
Author(s):  
Teresa M. Wilson ◽  
Hirofumi Tanaka
Keyword(s):  
Meta Analysis ◽  
Maximal Oxygen Consumption ◽  
Group Differences ◽  
Maximal Heart Rate ◽  
Maximal Aerobic Capacity ◽  
Cross Sectional ◽  
Physically Active ◽  
Age Related ◽  
Rate Of Decline ◽  
Exercise Status

Based on cross-sectional data, we recently reported that, in contrast to the prevailing view, the rate of decline in maximal oxygen consumption (V˙o 2 max) with age is greater in physically active compared with sedentary healthy women. We tested this hypothesis in men using a meta-analytic study ofV˙o 2 max values in the published literature. A total of 242 studies (538 subject groups and 13,828 subjects) met the inclusion criteria and were arbitrarily separated into sedentary (214 groups, 6,231 subjects), active (159 groups, 5,621 subjects), and endurance-trained (165 groups, 1,976 subjects) populations. Body fat percent increased with age in sedentary and active men ( P < 0.001), whereas no change was observed in endurance-trained men.V˙o 2 max was inversely and strongly related to age within each population ( r = −0.80 to −0.88, all P < 0.001) and was highest in endurance-trained and lowest in sedentary populations at any age. Absolute rates of decline inV˙o 2 max with age were not different ( P > 0.05) in sedentary (−4.0 ml ⋅ kg−1 ⋅ min−1 ⋅ decade−1), active (−4.0), and endurance-trained (−4.6) populations. Similarly, there were no group differences ( P > 0.05) in the relative (%) rates of decline inV˙o 2 max with advancing age (−8.7, −7.3, and −6.8%/decade, respectively). Maximal heart rate was inversely related to age within each population ( r = −0.88 to −0.93, all P < 0.001), but the rate of age-related reduction was not different among the populations. There was a significant decline in running mileage and speed with advancing age in the endurance-trained men. The present cross-sectional meta-analytic findings do not support the hypothesis that the rate of decline inV˙o 2 max with age is related to habitual aerobic exercise status in men.

scholarly journals Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging

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.

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

2019 ◽  
Vol 16 (17) ◽  
pp. 3074 ◽  
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.

Reconsidering the HbA1c Cutoff for Diabetes Diagnosis Based on a Large Chinese Cohort

2019 ◽  
Author(s):  
Jiying Qi ◽  
Yang Su ◽  
Qianqian Song ◽  
Zhaojun Ding ◽  
Min Cao ◽  
...  
Keyword(s):  
Positive Association ◽  
Diabetes Diagnosis ◽  
Middle Aged ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Aged Population ◽  
Diagnosis And Management ◽  
Age Related ◽  
The Difference ◽  
Hba1c Levels

Abstract Introduction The HbA1c has been considered as the ‘gold standard’ in diabetes diagnosis and management, however, age, gender and body mass index (BMI) might have certain effects on HbA1c. We are aiming to further investigate the correlation between age and HbA1c, and whether it was affected by gender and BMI. Methods A cross-sectional survey including 135,893 nondiabetic individuals who took the physical examination between 2013 and 2017 was conducted. The subjects were grouped by gender, age and BMI, and the interactive and independent effects of the 3 factors on the HbA1c were detected. The median and 95% confidence interval (CI) of HbA1c levels were calculated. Results The HbA1c levels gradually increased along with age, both in female and male, and there is a positive association between BMI and the HbA1c. The difference on HbA1c in gender was associated with both age and BMI, the age-related increase in HbAlc was accentuated in the subgroup with higher BMI, and there was a marked accentuation of the positive association between BMI and HbA1c as age increased. In almost all the young and middle-aged (aged 20–59) subgroups, the 97.5th percentiles of HbA1c levels were lower than 6.5%, suggesting that the single HbA1c cutoff value is probably not applicable to the young and middle-aged population. Conclusions We recommend that the effects of age, gender and BMI should be taken into consideration when using HbA1c for the diagnosis and management of diabetes, especially in the young and middle-aged population.

scholarly journals Insulin-related dietary indices predict 24-h urinary C-peptide in adult men

2020 ◽  
pp. 1-8
Author(s):  
Dong Hoon Lee ◽  
Edward L. Giovannucci ◽  
Fred K. Tabung
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Positive Association ◽  
Significant Positive Association ◽  
Cross Sectional ◽  
C Peptide ◽  
Adult Men ◽  
Dietary Index ◽  
Sectional Analysis ◽  
Dietary Indices

Abstract The dietary insulin index directly estimates the postprandial insulin secretion potential of foods, whereas the empirical dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemic potential of usual diets based on fasting plasma C-peptide, and is primarily reflective of insulin resistance. It is unknown whether these insulin-related indices are predictive of an integrated measure of insulin secretion. We conducted a cross-sectional analysis that included 293 non-diabetic men with 24-h urinary C-peptide data from the Men’s Lifestyle Validation Study. EDIH, dietary insulin index and dietary insulin load were calculated using validated FFQ. We conducted multivariable-adjusted linear regression to estimate relative and absolute concentrations of 24-h urinary C-peptide. In multivariable-adjusted models, we found a significant positive association between all three insulin-related dietary indices and 24-h urinary C-peptide (P < 0·05). Relative concentrations of 24-h urinary C-peptide per 1-sd increase in insulin-related dietary indices were 1·12 (95 % CI 1·02, 1·23) for EDIH, 1·18 (95 % CI 1·07, 1·29) for dietary insulin index and 1·16 (95 % CI 1·06, 1·27) for dietary insulin load. When we further adjusted for BMI, the association was attenuated for EDIH, to 1·07 (95 % CI 0·98, 1·16), and remained unchanged for dietary insulin index and dietary insulin load. In conclusion, EDIH, dietary insulin index and dietary insulin load were predictive of integrated insulin secretion assessed by 24-h urinary C-peptide. Findings after adjustment for BMI appear to confirm the relation of EDIH to insulin resistance and dietary insulin index/load to insulin secretion; the respective constructs of the two dietary indices.

scholarly journals The Association between Adiposity and the Risk of Glaucoma: A Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Weiming Liu ◽  
Jiawen Ling ◽  
Yiyi Chen ◽  
Yan Wu ◽  
Peirong Lu
Keyword(s):  
Web Of Science ◽  
Open Angle Glaucoma ◽  
Meta Analysis ◽  
Positive Association ◽  
Female Group ◽  
Abdominal Adiposity ◽  
Cross Sectional ◽  
Relative Risks ◽  
Potential Association ◽  
General Adiposity

Purpose. This meta-analysis was conducted to determine the potential association between adiposity and glaucoma incidence.Materials and Methods. A comprehensive literature search was performed in PubMed and ISI Web of Science. A meta-analysis was conducted using STATA software.Results. Fifteen eligible studies involving 2,445,980 individuals were included to investigate the association between adiposity and glaucoma incidence. The relative risks (RRs) were pooled with 95% confidence intervals (CI) by using a random-effects model. The pooled RR between adiposity and elevated intraocular pressure (IOP) was 1.73 (95% CI, 1.18–2.54), whereas that between adiposity and open-angle glaucoma (OAG) was 0.97 (95% CI, 0.83–1.13). The pooled RR between abdominal adiposity and glaucoma was 1.28 (95% CI, 1.15–1.41), whereas that between general adiposity and glaucoma was 1.09 (95% CI, 0.87–1.37). Results of subgroup analysis by sex indicated the association between adiposity and glaucoma in the female group (RR, 1.31; 95% CI, 1.05–1.64), but not in the male group (RR, 1.11; 95% CI, 0.77–1.60). The pooled RR of cohort studies and cross-sectional studies were 1.00 (95% CI, 0.84–1.20) and 1.22 (95% CI, 0.89–1.66), respectively.Conclusions.Adiposity has a higher risk of elevated IOP, and abdominal adiposity has a positive association with glaucoma, especially in female patients.

scholarly journals The Effects of Anti-retroviral Therapy on Epigenetic Age Acceleration Observed in HIV-1-infected Adults

2020 ◽  
Vol 5 (1) ◽  
pp. 291-311
Author(s):  
Mary E. Sehl ◽  
Tammy M. Rickabaugh ◽  
Roger Shih ◽  
Otoniel Martinez-Maza ◽  
Steve Horvath ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Epigenetic Clock ◽  
Time Points ◽  
Art Initiation ◽  
Age Related ◽  
Epigenetic Age ◽  
Significant Difference ◽  
Epigenetic Age Acceleration ◽  
Hiv 1 ◽  
Time Point

Background: HIV-1 infection is associated with acceleration of age-related methylation patterns in peripheral blood and brain of infected individuals although the relative contributions of HIV-1 infection versus its treatment to the observed accelerations in biological aging have not yet been investigated.Methods: In this longitudinal study of the effects of antiretroviral therapy (ART) on epigenetic aging patterns, we extracted DNA from peripheral blood mononuclear cells from 15 HIV-1-infected individuals infected at three time points: 6 months-1year pre-ART, 6-12 months post-initiation of ART, and 18-24 months after initiating ART. We compared these trajectories with those of 15 age-matched uninfected control participants at three time points with similar intervals. Methylation studies were performed using the Infinium methylation 450 arrays. We examined four epigenetic clock measurements: Age acceleration residual (AAR), Extrinsic (EEAA), Phenotypic (PEAA), and Grim (GEAA) epigenetic age acceleration. Weighted correlation network (WGCNA) analysis was used to identify clusters of highly co-methylated CpGs.Results: We found that prior to the initiation of ART all four epigenetic measures were significantly higher in HIV-1-infected individuals compared with uninfected individuals (P<0.001 for AAR, P=0.008 for EEAA, P=0.012 for GEAA, P<0.001 for PEAA using Wilcoxon rank sum tests between serostatus groups). These effects persisted after the initiation of ART, although the magnitude of these differences diminished. At 18-24 months post-ART initiation (time point 3), PEAA and GEAA were no longer significantly different between HIV-1-infected and uninfected individuals (P=0.059 for PEAA, P=0.11 for GEAA), while AAR and EEAA remained significantly higher in HIV-1-infected individuals compared with uninfected individuals. We further examined for global patterns of methylation differences between HIV-1-infected and uninfected at each time point, and found 14 groups of co-methylated CpGs that were significantly different between groups at baseline, and remained different after the initiation of ART.Conclusion: We confirm that epigenetic age acceleration associated with HIV-1 infection is most dramatic before ART initiation, and this observation is consistent across four epigenetic clock measurements, as well as in additional groups of co-methylated CpGs identified using WGCNA. Following initiation of ART, there is a partial reduction in age acceleration in all measures, with loss of any significant difference in PEAA and GEAA between serostatus groups. Our findings support the need for future studies examining for a link between epigenetic age acceleration and clinical outcomes in HIV-1-infected individuals.

scholarly journals Novel Epigenetic Clock for Fetal Brain Development Predicts Fetal Epigenetic Age for iPSCs and iPSC-Derived Neurons.

2020 ◽  
Author(s):  
Leonard C Steg ◽  
Gemma L Shireby ◽  
Jennifer Imm ◽  
Jonathan P Davies ◽  
Robert Flynn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Fetal Brain ◽  
Cell Types ◽  
Biological Research ◽  
Epigenetic Clock ◽  
Cellular Model ◽  
Neuronal Precursor Cells ◽  
Age Related ◽  
Epigenetic Age

Abstract Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the early stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age, and is has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons, here, we establish the fetal brain clock (FBC), a bespoke epigenetic clock trained in prenatal neurodevelopmental samples. Our data show that the FBC outperforms other established epigenetic clocks in predicting the age of fetal brain samples. We then applied the FBC to DNA methylation data of cellular datasets that have profiled iPSCs and iPSC-derived neuronal precursor cells and neurons and find that these cell types are characterized by a fetal epigenetic age. Furthermore, while differentiation from iPSCs to neurons significantly increases the epigenetic age, iPSC-neurons are still predicted as having fetal epigenetic age. Together our findings reiterate the need for better understanding of the limitations of existing epigenetic clocks for answering biological research questions and highlight a potential limitation of iPSC-neurons as a cellular model for the research of age-related diseases as they might not fully recapitulate an aged phenotype.

scholarly journals Novel epigenetic clock for fetal brain development predicts fetal epigenetic age for iPSCs and iPSC-derived neurons

2020 ◽  
Author(s):  
Leonard C. Steg ◽  
Gemma L. Shireby ◽  
Jennifer Imm ◽  
Jonathan P. Davies ◽  
Robert Flynn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Fetal Brain ◽  
Cell Types ◽  
Biological Research ◽  
Epigenetic Clock ◽  
Cellular Model ◽  
Neuronal Precursor Cells ◽  
Age Related ◽  
Epigenetic Age

AbstractInduced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the early stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age, and is has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons, here, we establish the fetal brain clock (FBC), a bespoke epigenetic clock trained in prenatal neurodevelopmental samples. Our data show that the FBC outperforms other established epigenetic clocks in predicting the age of fetal brain samples. We then applied the FBC to DNA methylation data of cellular datasets that have profiled iPSCs and iPSC-derived neuronal precursor cells and neurons and find that these cell types are characterized by a fetal epigenetic age. Furthermore, while differentiation from iPSCs to neurons significantly increases the epigenetic age, iPSC-neurons are still predicted as having fetal epigenetic age. Together our findings reiterate the need for better understanding of the limitations of existing epigenetic clocks for answering biological research questions and highlight a potential limitation of iPSC-neurons as a cellular model for the research of age-related diseases as they might not fully recapitulate an aged phenotype.

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