Cerebral white matter hyperintensities on MRI and acceleration of epigenetic aging: the atherosclerosis risk in
Abhay Raina1, Xiaoping Zhao1, Megan L Grove2
1Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street, 77030 Houston, TX USA.
Background:
Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration, which represents the deviation of the DNA methylation-predicted age from the chronologic age.
Results:
In this cross-sectional observational study of 713 African-American participants of the Atherosclerosis Risk in Communities study, aged 51-73 years, estimates of predicted age were obtained based on two algorithms (Hannum et al. and Horvath) from DNA methylation measured using the Illumina HM450 array on genomic DNA extracted from blood. Age acceleration, calculated as the residual values from the regression of each of the predicted age measures onto the chronologic age, was significantly associated with WMH burden after accounting for chronologic age and sex, body mass index, systolic blood pressure, hypertension, diabetes, current smoking, and blood cell composition, and results were similar for either Hannum et al.- or Horvath-derived estimates (P = 0.016 and 0.026). An age acceleration increase by 1 year was associated with an increase of WMH burden by ~1 grade. To shed light on possible biological mechanisms underlying this association, we conducted a genome-wide association study of age acceleration and identified four loci harboring genes implicated in hemostasis, cell proliferation, protein degradation, and histone methylation. However, none of these loci were associated with WMH burden.
Conclusions:
In this population-based study of middle-aged to older African-American adults, we report an association between accelerated epigenetic aging and increased WMH burden, independent of known risk factors, including chronologic age. Additional studies are needed to clarify whether DNA methylation age reflects biological mechanisms implicated in the aging of the cerebral white matter.
Insights
Accelerated epigenetic aging is linked to greater white matter hyperintensities (WMH) in older African Americans. This association persists even when considering factors like chronological age and other health risks.
Area of Science:
- Epigenetics
- Neuroimaging
- Aging research
Background:
- Cerebral white matter hyperintensities (WMH) are markers of brain vascular injury associated with aging, stroke, and dementia.
- DNA methylation age acceleration is a biomarker reflecting the difference between predicted epigenetic age and chronological age.
Purpose of the Study:
- To investigate the association between DNA methylation age acceleration and the burden of cerebral white matter hyperintensities (WMH).
Main Methods:
- Cross-sectional observational study of 713 African-American adults (aged 51-73).
- DNA methylation was measured using the Illumina HM450 array.
- Age acceleration was calculated as residuals from regression of DNA methylation-predicted age on chronological age.
Main Results:
- Accelerated DNA methylation age was significantly associated with increased WMH burden, independent of chronological age and other risk factors.
- Each 1-year increase in age acceleration correlated with approximately a 1-grade increase in WMH burden.
- Genome-wide association study identified loci related to aging but not directly associated with WMH burden.
Conclusions:
- Accelerated epigenetic aging is associated with increased WMH burden in middle-aged to older African Americans.
- This relationship is independent of established risk factors for cerebrovascular disease.
- Further research is needed to elucidate the biological mechanisms linking epigenetic aging and cerebral white matter aging.
More Related Videos
07:30Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
05:12A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
Related Concept Videos
01:30Coronary Artery Disease I: Introduction
01:30Atherosclerosis I: Introduction
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
01:29Alzheimer Disease l: Introduction