Association of Epigenetic Metrics of Biological Age With Cortical Thickness

Proskovec, Amy L.; Rezich, Michael T; Morsey, Brenda; Wang, Tina; Ideker, Trey; Swindells, Susan; Fox, Howard S.; Wilson, Tony W.

doi:10.1001/jamanetworkopen.2020.15428

Cited by 25 publications

(16 citation statements)

References 58 publications

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“…Such widespread age-related reductions in CT are in concordance with previous reports revealing age-related thinning across the majority of the cortex with the most robust changes regarding bilateral frontal cortices, superior temporal regions, and supramarginal gyri. These changes are believed to be related to a decrease in dendritic density of neurons as well as changes in cortical myelination ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cortical indices such as CT, GI, SC, and FS have been reported to change in older people and in neurodegenerative diseases ( 11 , 12 ). In healthy adults, age-related thinning is observed across the majority of the cortex but is generally more robust in bilateral frontal cortices, superior temporal regions, and supramarginal gyri ( 13 ). Several studies have shown that global cortical gyrification reflected by GI decreases with age in several cross-sectional samples, and topography of these changes is different from CT ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Novel Volumetric and Surface-Based Magnetic Resonance Indices of the Aging Brain – Does Male and Female Brain Age in the Same Way?

et al. 2021

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Introduction: Novel post-processing methods allow not only for assessment of brain volumetry or cortical thickness based on magnetic resonance imaging (MRI) but also for more detailed analysis of cortical shape and complexity using parameters such as sulcal depth, gyrification index, or fractal dimension. The aim of this study was to analyze changes in brain volumetry and other cortical indices during aging in men and women.Material and Methods: Material consisted of 697 healthy volunteers (aged 38–80 years; M/F, 264/443) who underwent brain MRI using a 1.5-T scanner. Voxel-based volumetry of total gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was performed followed by assessment of cortical parameters [cortical thickness (CT), sulcal depth (SD), gyrification index (GI), and fractal dimension (FD)] in 150 atlas locations using surface-based morphometry with a region-based approach. All parameters were compared among seven age groups (grouped every 5 years) separately for men and women. Additionally, percentile curves for men and women were provided for total volumes of GM, WM, and CSF.Results: In men and women, a decrease in GM and WM volumes and an increase in CSF volume seem to progress slowly since the age of 45. In men, significant GM and WM loss as well as CSF increase start above 55 years of age, while in women, significant GM loss starts above 50 and significant WM loss as well as CSF increase above 60. CT was found to significantly decrease with aging in 39% of locations in women and in 36% of locations in men, SD was found to increase in 13.5% of locations in women and in 1.3% of locations in men, GI was decreased in 3.4% of locations in women and in 2.0% of locations in men, and FD was changed in 2.7% of locations in women compared to 2.0% in men.Conclusions: Male and female brains start aging at the similar age of 45. Compared to men, in women, the cortex is affected earlier and in the more complex pattern regarding not only cortical loss but also other alterations within the cortical shape, with relatively longer sparing of WM volume.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Volumetric and Surface-Based Magnetic Resonance Indices of the Aging Brain – Does Male and Female Brain Age in the Same Way?

et al. 2021

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“…Advanced DNAm age is a biomarker for increased risk for premature disease onset, including neuropathology, such as Alzheimer's disease ( Levine et al, 2015 ) and reduced morphological integrity of the brain ( Proskovec et al, 2020 ; Wolf et al, 2019 ). Despite the direct role of DNAm on gene expression, no study to date has evaluated the expression correlates of slowed or advanced DNAm age in neural tissue.…”

Section: Discussionmentioning

confidence: 99%

Gene expression correlates of advanced epigenetic age and psychopathology in postmortem cortical tissue

Wolf

Zhao

Hawn

et al. 2021

Neurobiology of Stress

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Psychiatric stress has been associated with accelerated epigenetic aging (i.e., when estimates of cellular age based on DNA methylation exceed chronological age) in both blood and brain tissue. Little is known about the downstream biological effects of accelerated epigenetic age on gene expression. In this study we examined associations between DNA methylation-derived estimates of cellular age that range from decelerated to accelerated relative to chronological age (“DNAm age residuals”) and transcriptome-wide gene expression. This was examined using tissue from three post-mortem cortical regions (ventromedial and dorsolateral prefrontal cortex and motor cortex, n = 97) from the VA National PTSD Brain Bank. In addition, we examined how posttraumatic stress disorder (PTSD) and alcohol-use disorders (AUD) moderated the association between DNAm age residuals and gene expression. Transcriptome-wide results across brain regions, psychiatric diagnoses, and cohorts (full sample and male and female subsets) revealed experiment-wide differential expression of 11 genes in association with PTSD or AUD in interaction with DNAm age residuals. This included the inflammation-related genes IL1B , RCOR2 , and GCNT1 . Candidate gene class analyses and gene network enrichment analyses further supported differential expression of inflammation/immune gene networks as well as glucocorticoid, circadian, and oxidative stress-related genes. Gene co-expression network modules suggested enrichment of myelination related processes and oligodendrocyte enrichment in association with DNAm age residuals in the presence of psychopathology. Collectively, results suggest that psychiatric stress accentuates the association between advanced epigenetic age and expression of inflammation genes in the brain. This highlights the role of inflammatory processes in the pathophysiology of accelerated cellular aging and suggests that inflammatory pathways may link accelerated cellular aging to premature disease onset and neurodegeneration, particularly in stressed populations. This suggests that anti-inflammatory interventions may be an important direction to pursue in evaluating ways to prevent or delay cellular aging and increase resilience to diseases of aging.

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“…We used a 3D fast field echo sequence with these parameters: TR: 8.09 ms; TE: 3.7 ms; the field of view: 24 cm; matrix: 256 × 256; slice thickness: 1 mm with no gap; in‐plane resolution: 0.9375 × 0.9375 mm; sense factor: 1.5. The details of our MRI data processing pipeline are available (Proskovec et al, 2020). Briefly, we used the Computational Anatomy Toolbox (CAT12 v12.6; Gaser & Dahnke, 2016) within SPM12 to conduct standard surface‐based morphometry (SBM) on the high‐resolution structural data.…”

Section: Methodsmentioning

confidence: 99%

Impact of HIV‐infection on human somatosensory processing, spontaneous cortical activity, and cortical thickness: A multimodal neuroimaging approach

Casagrande

Lew

Taylor

et al. 2021

Human Brain Mapping

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HIV‐infection has been associated with widespread alterations in brain structure and function, although few studies have examined whether such aberrations are co‐localized and the degree to which clinical and cognitive metrics are related. We examine this question in the somatosensory system using high‐resolution structural MRI (sMRI) and magnetoencephalographic (MEG) imaging of neural oscillatory activity. Forty‐four participants with HIV (PWH) and 55 demographically‐matched uninfected controls completed a paired‐pulse somatosensory stimulation paradigm during MEG and underwent 3T sMRI. MEG data were transformed into the time‐frequency domain; significant sensor level responses were imaged using a beamformer. Virtual sensor time series were derived from the peak responses. These data were used to compute response amplitude, sensory gating metrics, and spontaneous cortical activity power. The T1‐weighted sMRI data were processed using morphological methods to derive cortical thickness values across the brain. From these, the cortical thickness of the tissue coinciding with the peak response was estimated. Our findings indicated both PWH and control exhibit somatosensory gating, and that spontaneous cortical activity was significantly stronger in PWH within the left postcentral gyrus. Interestingly, within the same tissue, PWH also had significantly reduced cortical thickness relative to controls. Follow‐up analyses indicated that the reduction in cortical thickness was significantly correlated with CD4 nadir and mediated the relationship between HIV and spontaneous cortical activity within the left postcentral gyrus. These data indicate that PWH have abnormally strong spontaneous cortical activity in the left postcentral gyrus and such elevated activity is driven by locally reduced cortical gray matter thickness.

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Association of Epigenetic Metrics of Biological Age With Cortical Thickness

Cited by 25 publications

References 58 publications

Novel Volumetric and Surface-Based Magnetic Resonance Indices of the Aging Brain – Does Male and Female Brain Age in the Same Way?

Novel Volumetric and Surface-Based Magnetic Resonance Indices of the Aging Brain – Does Male and Female Brain Age in the Same Way?

Gene expression correlates of advanced epigenetic age and psychopathology in postmortem cortical tissue

Impact of HIV‐infection on human somatosensory processing, spontaneous cortical activity, and cortical thickness: A multimodal neuroimaging approach

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