scholarly journals Accelerated aging in the brain, epigenetic aging in blood, and polygenic risk for schizophrenia

2021 ◽  
Vol 231 ◽  
pp. 189-197
Author(s):  
Jalmar Teeuw ◽  
Anil P.S. Ori ◽  
Rachel M. Brouwer ◽  
Sonja M.C. de Zwarte ◽  
Hugo G. Schnack ◽  
...  
Keyword(s):  
Accelerated Aging ◽  
Polygenic Risk ◽  
Epigenetic Aging ◽  
The Brain

scholarly journals Accelerated aging in the brain, epigenetic aging in blood, and polygenic risk for schizophrenia

2020 ◽  
Author(s):  
Jalmar Teeuw ◽  
Anil PS Ori ◽  
Rachel M Brouwer ◽  
Sonja MC de Zwarte ◽  
Hugo G Schnack ◽  
...  
Keyword(s):  
Brain Aging ◽  
Accelerated Aging ◽  
Disease Status ◽  
Risk Scores ◽  
Brain Images ◽  
Polygenic Risk ◽  
Acceleration Rate ◽  
Epigenetic Aging ◽  
Brain Age ◽  
The Brain

Schizophrenia patients show signs of accelerated aging in cognitive and physiological domains. Both schizophrenia and accelerated aging, as measured by MRI brain images and epigenetic clocks, are correlated with increased mortality. However, the association between these aging measures have not yet been studied in schizophrenia patients. In schizophrenia patients and healthy subjects, accelerated aging was assessed in brain tissue using a longitudinal MRI (N=715 scans; mean scan interval 3.4 year) and in blood using two epigenetic age clocks (N=172). Differences ('gaps') between estimated ages and chronological ages were calculated, as well as the acceleration rate of brain aging. The correlations between these aging measures as well as with polygenic risk scores for schizophrenia (PRS; N=394) were investigated. Brain aging and epigenetic aging were not significantly correlated. Polygenic risk for schizophrenia was significantly correlated with brain age gap, brain age acceleration rate, and negatively correlated with DNAmAge gap, but not with PhenoAge gap. However, after controlling for disease status and multiple comparisons correction, these effects were no longer significant. Our results imply that the (accelerated) aging observed in the brain and blood reflect distinct biological processes. Our findings will require replication in a larger cohort.

scholarly journals Is Hypertension Associated With an Accelerated Aging of the Brain?

Hypertension ◽  
2014 ◽  
Vol 63 (5) ◽  
pp. 894-903 ◽  
Author(s):  
Christophe Tzourio ◽  
Stéphane Laurent ◽  
Stéphanie Debette
Keyword(s):  
Accelerated Aging ◽  
The Brain

Accelerated aging of the brain transcriptome by the common chemotherapeutic doxorubicin

2021 ◽  
pp. 111451
Author(s):  
Alyssa N. Cavalier ◽  
Zachary S. Clayton ◽  
David A. Hutton ◽  
Devin Wahl ◽  
Julie A. Reisz ◽  
...  
Keyword(s):  
Accelerated Aging ◽  
Brain Transcriptome ◽  
The Common ◽  
The Brain

scholarly journals Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization

2021 ◽  
Author(s):  
Zhiqiang Sha ◽  
Dick Schijven ◽  
Clyde Francks
Keyword(s):  
Sex Differences ◽  
Executive Functions ◽  
Autism Spectrum ◽  
Brain Asymmetry ◽  
Risk Scores ◽  
Imaging Data ◽  
Polygenic Risk ◽  
Left Right Asymmetry ◽  
The Uk ◽  
The Brain

AbstractAutism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing versus empathizing cognitive styles, with resemblances to male versus female average sex differences. Left-right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes, and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores (PRS) for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness and subcortical volume measures in 32,256 participants from the UK Biobank. PRS for the two disorders were positively correlated (r=0.08, p=7.13×10−50), and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each PRS was associated with multivariate brain asymmetry after adjusting for sex, ASD PRS r=0.03, p=2.17×10−9, schizophrenia PRS r=0.04, p=2.61×10−11, but the multivariate patterns were mostly distinct for the two PRS, and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both PRS were associated with asymmetries of regions important for language and executive functions, consistent with behavioural associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risk for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.

scholarly journals Neurogenesis and brain aging

2019 ◽  
Vol 30 (6) ◽  
pp. 573-580 ◽  
Author(s):  
Nickolay K. Isaev ◽  
Elena V. Stelmashook ◽  
Elisaveta E. Genrikhs
Keyword(s):  
Brain Aging ◽  
Werner Syndrome ◽  
Accelerated Aging ◽  
Normal Aging ◽  
Postnatal Period ◽  
Human Aging ◽  
Distinctive Features ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome ◽  
The Brain

AbstractHuman aging affects the entire organism, but aging of the brain must undoubtedly be different from that of all other organs, as neurons are highly differentiated postmitotic cells, for the majority of which the lifespan in the postnatal period is equal to the lifespan of the entire organism. In this work, we examine the distinctive features of brain aging and neurogenesis during normal aging, pathological aging (Alzheimer’s disease), and accelerated aging (Hutchinson-Gilford progeria syndrome and Werner syndrome).

scholarly journals Schizophrenia is characterized by age- and sex-specific effects on epigenetic aging

2019 ◽  
Author(s):  
Anil P.S. Ori ◽  
Loes M. Olde Loohuis ◽  
Jerry Guintivano ◽  
Eilis Hannon ◽  
Emma Dempster ◽  
...  
Keyword(s):  
Accelerated Aging ◽  
Disease Status ◽  
Risk Scores ◽  
Chronological Age ◽  
Biological Aging ◽  
Disease Trajectory ◽  
Clinical Biomarkers ◽  
Age Related ◽  
Epigenetic Aging ◽  
Increased Risk

AbstractSchizophrenia (SCZ) is a severe mental illness that is associated with an increased prevalence of age-related disability and morbidity compared to the general population. An accelerated aging process has therefore been hypothesized as a component of the SCZ disease trajectory. Here, we investigated differential aging using three DNA methylation (DNAm) clocks (i.e. Hannum, Horvath, Levine) in a multi-cohort SCZ whole blood sample consisting of 1,100 SCZ cases and 1,200 controls. It is known that all three DNAm clocks are highly predictive of chronological age and capture different features of biological aging. We found that blood-based DNAm aging is significantly altered in SCZ with age- and sexspecific effects that differ between clocks and map to distinct chronological age windows. Most notably, the predicted phenotypic age (Levine clock) in female cases, starting at age 36 and beyond, is 3.21 years older compared to matching control subjects (95% CI: 1.92-4.50, P=1.3e-06) explaining 7.7% of the variance in disease status. Female cases with high SCZ polygenic risk scores present the highest age acceleration in this age group with +7.03 years (95% CI: 3.87-10.18, P=1.7E-05). Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings suggests that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. These results provide new biological insights into the aging landscape of SCZ with age- and sexspecific effects and warrant further investigations into the potential of DNAm clocks as clinical biomarkers that may help with disease management in schizophrenia.

scholarly journals Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain

2021 ◽  
Vol 12 ◽  
Author(s):  
Feitong Shi ◽  
Yudan He ◽  
Yao Chen ◽  
Xinman Yin ◽  
Xianzheng Sha ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Extracellular Fluid ◽  
Accelerated Aging ◽  
Enrichment Analysis ◽  
Supervised Machine Learning ◽  
System Level ◽  
Aging Brain ◽  
Cellular Homeostasis ◽  
Epigenetic Aging ◽  
Aging Mechanisms

Background: Neurodegenerative Diseases (NDs) are age-dependent and include Alzheimer’s disease (AD), Parkinson’s disease (PD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), and so on. There have been numerous studies showing that accelerated aging is closely related (even the driver of) ND, thus promoting imbalances in cellular homeostasis. However, the mechanisms of how different ND types are related/triggered by advanced aging are still unclear. Therefore, there is an urgent need to explore the potential markers/mechanisms of different ND types based on aging acceleration at a system level.Methods: AD, PD, PSP, FTD, and aging markers were identified by supervised machine learning methods. The aging acceleration differential networks were constructed based on the aging score. Both the enrichment analysis and sensitivity analysis were carried out to investigate both common and specific mechanisms among different ND types in the context of aging acceleration.Results: The extracellular fluid, cellular metabolisms, and inflammatory response were identified as the common driving factors of cellular homeostasis imbalances during the accelerated aging process. In addition, Ca ion imbalance, abnormal protein depositions, DNA damage, and cytoplasmic DNA in macrophages were also revealed to be special mechanisms that further promote AD, PD, PSP, and FTD, respectively.Conclusion: The accelerated epigenetic aging mechanisms of different ND types were integrated and compared through our computational pipeline.

scholarly journals The efficacy of obesity polygenic risk scores in an autistic population

2019 ◽  
Author(s):  
David Y. Zhang ◽  
Nathan P. Palmer ◽  
Chuan Hong ◽  
Luwan Zhang ◽  
Samuel G. Finlayson ◽  
...  
Keyword(s):  
European Ancestry ◽  
Risk Scores ◽  
Great Promise ◽  
Polygenic Risk ◽  
Clinical Diagnoses ◽  
Prevalence Of Obesity ◽  
Different Populations ◽  
The Difference ◽  
The Brain ◽  
A Current

AbstractPolygenic risk scores (PRS) bear great promise in understanding complex diseases and improving clinical diagnoses, but the competency of these risk scores in different populations is known to vary significantly, especially between those of European ancestry and those of other ethnic ancestries. Additionally, the applicability of these risk scores across populations different by disease, instead of ethnicity, is poorly understood. A current and largely unexplored population for the accuracy of PRS is that of individuals with autism. Combined with the increased prevalence of obesity in autistic populations, we seek to evaluate the difference in efficacy of PRS for obesity in autistic versus non-autistic populations. We show that genetic variants strongly associated with obesity in non-autistic populations are significantly less representative of the disease in autistic populations. Rather, these cases of obesity phenocopies in patients with autism may follow a different and non-conventional mechanism of action involving the regulation of oxytocin in the brain among other potential behavioral factors. Our findings elucidate the limits of PRS across populations contrasting by disease and suggest that obesity may be regulated differently in individuals with autism as compared to those without autism.

scholarly journals Psychological and biological resilience modulates the effects of stress on epigenetic aging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zachary M. Harvanek ◽  
Nia Fogelman ◽  
Ke Xu ◽  
Rajita Sinha
Keyword(s):  
Insulin Resistance ◽  
Emotion Regulation ◽  
Accelerated Aging ◽  
Self Control ◽  
Biological Age ◽  
Healthy Population ◽  
Cumulative Stress ◽  
Epigenetic Aging ◽  
Resilience Factors ◽  
The Impact

AbstractOur society is experiencing more stress than ever before, leading to both negative psychiatric and physical outcomes. Chronic stress is linked to negative long-term health consequences, raising the possibility that stress is related to accelerated aging. In this study, we examine whether resilience factors affect stress-associated biological age acceleration. Recently developed “epigenetic clocks” such as GrimAge have shown utility in predicting biological age and mortality. Here, we assessed the impact of cumulative stress, stress physiology, and resilience on accelerated aging in a community sample (N = 444). Cumulative stress was associated with accelerated GrimAge (P = 0.0388) and stress-related physiologic measures of adrenal sensitivity (Cortisol/ACTH ratio) and insulin resistance (HOMA). After controlling for demographic and behavioral factors, HOMA correlated with accelerated GrimAge (P = 0.0186). Remarkably, psychological resilience factors of emotion regulation and self-control moderated these relationships. Emotion regulation moderated the association between stress and aging (P = 8.82e−4) such that with worse emotion regulation, there was greater stress-related age acceleration, while stronger emotion regulation prevented any significant effect of stress on GrimAge. Self-control moderated the relationship between stress and insulin resistance (P = 0.00732), with high self-control blunting this relationship. In the final model, in those with poor emotion regulation, cumulative stress continued to predict additional GrimAge Acceleration even while accounting for demographic, physiologic, and behavioral covariates. These results demonstrate that cumulative stress is associated with epigenetic aging in a healthy population, and these associations are modified by biobehavioral resilience factors.

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