Characterization of cerebrospinal fluid DNA methylation age during the acute recovery period following aneurysmal subarachnoid hemorrhage

Abstract Background Biological aging may occur at different rates than chronological aging due to genetic, social, and environmental factors. DNA methylation (DNAm) age is thought to be a reliable measure of accelerated biological aging which has been linked to an array of poor health outcomes. Given the importance of chronological age in recovery following aneurysmal subarachnoid hemorrhage (aSAH), a type of stroke, DNAm age may also be an important biomarker of outcomes, further improving predictive models. Cerebrospinal fluid (CSF) is a unique tissue representing the local central nervous system environment post-aSAH. However, the validity of CSF DNAm age is unknown, and it is unclear which epigenetic clock is ideal to compute CSF DNAm age, particularly given changes in cell type heterogeneity (CTH) during the acute recovery period. Further, the stability of DNAm age post-aSAH, specifically, has not been examined and may improve our understanding of patient recovery post-aSAH. Therefore, the purpose of this study was to characterize CSF DNAm age over 14 days post-aSAH using four epigenetic clocks. Results Genome-wide DNAm data were available for two tissues: (1) CSF for N = 273 participants with serial sampling over 14 days post-aSAH (N = 850 samples) and (2) blood for a subset of n = 72 participants at one time point post-aSAH. DNAm age was calculated using the Horvath, Hannum, Levine, and “Improved Precision” (Zhang) epigenetic clocks. “Age acceleration” was computed as the residuals of DNAm age regressed on chronological age both with and without correcting for CTH. Using scatterplots, Pearson correlations, and group-based trajectory analysis, we examined the relationships between CSF DNAm age and chronological age, the concordance between DNAm ages calculated from CSF versus blood, and the stability (i.e., trajectories) of CSF DNAm age acceleration over time during recovery from aSAH. We observed moderate to strong correlations between CSF DNAm age and chronological age (R = 0.66 [Levine] to R = 0.97 [Zhang]), moderate to strong correlations between DNAm age in CSF versus blood (R = 0.69 [Levine] to R = 0.98 [Zhang]), and stable CSF age acceleration trajectories over 14 days post-aSAH in the Horvath and Zhang clocks (unadjusted for CTH), as well as the Hannum clock (adjusted for CTH). Conclusions CSF DNAm age was generally stable post-aSAH. Although correlated, CSF DNAm age differs from blood DNAm age in the Horvath, Hannum, and Levine clocks, but not in the Zhang clock. Taken together, our results suggest that, of the clocks examined here, the Zhang clock is the most robust to CTH and is recommended for use in complex tissues such as CSF.

Download Full-text

Increased concentration of atrial natriuretic factor in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage and raised intracranial pressure

Neurosurgery ◽

10.1097/00006123-198807000-00003 ◽

1988 ◽

Vol 23 (1) ◽

pp. 16???9

Author(s):

T D??czi ◽

F Jo?? ◽

M Vecserny??s ◽

M Bodosi

Keyword(s):

Cerebrospinal Fluid ◽

Subarachnoid Hemorrhage ◽

Intracranial Pressure ◽

Atrial Natriuretic Factor ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Raised Intracranial Pressure ◽

Natriuretic Factor ◽

Atrial Natriuretic

Download Full-text

Racial Differences in DNA Methylation-Based Age Acceleration in Preeclamptic and Normotensive Pregnancy

10.1101/2020.09.30.20204883 ◽

2020 ◽

Author(s):

Lacey W. Heinsberg ◽

Mitali Ray ◽

Yvette P. Conley ◽

James M. Roberts ◽

Arun Jeyabalan ◽

...

Keyword(s):

Dna Methylation ◽

Racial Disparities ◽

Small Sample ◽

Cellular Aging ◽

Neonatal Outcomes ◽

Chronological Age ◽

Biological Aging ◽

Cell Type ◽

Increased Risk ◽

Dna Methylation Age

ABSTRACTBackgroundPreeclampsia is a leading cause of maternal and neonatal morbidity and mortality. Chronological age and race are associated with increased risk of preeclampsia; however, the pathophysiology of preeclampsia and how these risk factors impact its development, are not entirely understood. This gap precludes clinical interventions to prevent preeclampsia occurrence or to address stark racial disparities in maternal and neonatal outcomes. Of note, cellular aging rates can differ between individuals and chronological age is often a poor surrogate of biological age. DNA methylation age provides a marker of biological aging, and those with a DNA methylation age greater than their chronological age have ‘age acceleration’. Examining age acceleration in the context of preeclampsia status, and race, could strengthen our understanding of preeclampsia pathophysiology, inform future interventions to improve maternal/neonatal outcomes, and provide insight to racial disparities across pregnancy.ObjectivesThe purpose of this exploratory study was to examine associations between age acceleration, preeclampsia status, and race across pregnancy.Study designThis was a longitudinal, observational, case-control study of 56 pregnant individuals who developed preeclampsia (n=28) or were normotensive controls (n=28). Peripheral blood samples were collected at trimester-specific time points and genome-wide DNA methylation data were generated using the Infinium MethylationEPIC Beadchip. DNA methylation age was estimated using the Elastic Net ‘Improved Precision’ clock and age acceleration was computed as Δage, the difference between DNA methylation age and chronological age. DNA methylation age was compared with chronological age using scatterplots and Pearson correlations, while considering preeclampsia status and race. The relationships between preeclampsia status, race, and Δage were formally tested using multiple linear regression, while adjusting for pre-pregnancy body mass index, chronological age, and (chronological age)2. Regressions were performed both with and without consideration of cell-type heterogeneity.ResultsWe observed strong correlations between chronological age and DNA methylation age in all trimesters, ranging from R=0.91-0.95 in cases and R=0.86-0.90 in controls. We observed significantly stronger correlations between chronological age and DNA methylation age in White versus Black participants ranging from R=0.89-0.98 in White participants and R=0.77-0.83 in Black participants. We observed no association between Δage and preeclampsia status within trimesters. However, even while controlling for covariates, Δage was higher in trimester 1 in participants with higher pre-pregnancy BMI (β=0.12, 95% CI=0.02 to 0.22, p=0.02) and lower in Black participants relative to White participants in trimesters 2 (β=−2.68, 95% CI=−4.43 to −0.94, p=0.003) and 3 (β=−2.10, 95% CI=−4.03 to −0.17, p=0.03). When controlling for cell-type heterogeneity, the observations with BMI in trimester 1 and race in trimester 2 persisted.ConclusionsWe report no association between Δage and preeclampsia status, although there were associations with pre-pregnancy BMI and race. In particular, our findings in a small sample demonstrate the need for additional studies to not only investigate the complex pathophysiology of preeclampsia, but also the relationship between race and biological aging, which could provide further insight into racial disparities in pregnancy and birth. Future efforts to confirm these findings in larger samples, including exploration and applications of other epigenetic clocks, is needed.

Download Full-text

Epigenetic clock and DNA methylation studies of roe deer in the wild

10.1101/2020.09.21.306613 ◽

2020 ◽

Author(s):

Jean-François Lemaître ◽

Benjamin Rey ◽

Jean-Michel Gaillard ◽

Corinne Régis ◽

Emmanuelle Gilot ◽

...

Keyword(s):

Dna Methylation ◽

Evolutionary Biology ◽

Roe Deer ◽

Chronological Age ◽

Epigenetic Clock ◽

Aging Effects ◽

Methylation Array ◽

Biomarkers Of Aging ◽

Epigenetic Age ◽

The Relationship

AbstractDNA methylation-based biomarkers of aging (epigenetic clocks) promise to lead to new insights in the evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic aging effects in wild species. In this study, we took advantage of a unique long-term (>40 years) longitudinal monitoring of individual roe deer (Capreolus capreolus) living in two wild populations (Chizé and Trois Fontaines, France) facing different ecological contexts to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n=90 blood samples using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation-based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age through the use of sex-specific epigenetic clocks. Our results highlight that both populations and sex influence the epigenetic age, with the bias toward a stronger male average age acceleration (i.e. differences between epigenetic age and chronological ages) particularly pronounced in the population facing harsh environmental conditions. Further, we identify the main sites of epigenetic alteration that have distinct aging patterns across the two sexes. These findings open the door to promising avenues of research at the crossroad of evolutionary biology and biogerontology.

Download Full-text

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.

Download Full-text