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Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.


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Journal ArticleDOI
19 Jun 2015-PLOS ONE
TL;DR: The finding suggests the significance of epigenetic regulation of this posttranslational modification pathway in the aging brain, and identifies significant ‘aging-segments’, which are clusters of nearby CpGs that respond to aging by similar DNA methylation changes.
Abstract: Understanding the fundamental dynamics of epigenome variation during normal aging is critical for elucidating key epigenetic alterations that affect development, cell differentiation and diseases. Advances in the field of aging and DNA methylation strongly support the aging epigenetic drift model. Although this model aligns with previous studies, the role of other epigenetic marks, such as histone modification, as well as the impact of sampling specific CpGs, must be evaluated. Ultimately, it is crucial to investigate how all CpGs in the human genome change their methylation with aging in their specific genomic and epigenomic contexts. Here, we analyze whole genome bisulfite sequencing DNA methylation maps of brain frontal cortex from individuals of diverse ages. Comparisons with blood data reveal tissue-specific patterns of epigenetic drift. By integrating chromatin state information, divergent degrees and directions of aging-associated methylation in different genomic regions are revealed. Whole genome bisulfite sequencing data also open a new door to investigate whether adjacent CpG sites exhibit coordinated DNA methylation changes with aging. We identified significant ‘aging-segments’, which are clusters of nearby CpGs that respond to aging by similar DNA methylation changes. These segments not only capture previously identified aging-CpGs but also include specific functional categories of genes with implications on epigenetic regulation of aging. For example, genes associated with development are highly enriched in positive aging segments, which are gradually hyper-methylated with aging. On the other hand, regions that are gradually hypo-methylated with aging (‘negative aging segments’) in the brain harbor genes involved in metabolism and protein ubiquitination. Given the importance of protein ubiquitination in proteome homeostasis of aging brains and neurodegenerative disorders, our finding suggests the significance of epigenetic regulation of this posttranslational modification pathway in the aging brain. Utilizing aging segments rather than individual CpGs will provide more comprehensive genomic and epigenomic contexts to understand the intricate associations between genomic neighborhoods and developmental and aging processes. These results complement the aging epigenetic drift model and provide new insights.

28 citations

Journal ArticleDOI
TL;DR: There is a need to improve neuronal communication in the brain in aging, which is habitually destabilized by enhanced oxidative stress, inflammation and toxic protein accumula -tion that can ultimately lead to death of neurons, disease pathologies and behavioral deficits.
Abstract: . Although healthy aging may have previ-ously been regarded as preventing wrinkles or reducing heart disease risk, as the inci-dences of neurological diseases are skyrock -eting in tandem with the economic burden of long-term care for the elderly, interest in the aging brain is growing. Dementia is one consequence of brain aging, with con -comitant behavioral deficits in motor and cognitive function. Therefore, there is a need to improve neuronal communication in the brain in aging, which is habitually destabilized by enhanced oxidative stress, inflammation and toxic protein accumula -tion. These factors can ultimately lead to death of neurons, disease pathologies and behavioral deficits.Neurodegeneration is highly debilitating in nature, and the underlying brain pathol -ogy may go undetected prior to the presen -tation of symptoms or diagnosis

28 citations

Journal ArticleDOI
06 Jul 2021
TL;DR: In this article, the authors discuss white matter changes, with focus on oligodendrocyte lineage cells and their ability to produce and maintain myelin to support normal brain homoeostasis.
Abstract: More than half of the human brain volume is made up of white matter: regions where axons are coated in myelin, which primarily functions to increase the conduction speed of axon potentials. White matter volume significantly decreases with age, correlating with cognitive decline. Much research in the field of non-pathological brain aging mechanisms has taken a neuron-centric approach, with relatively little attention paid to other neural cells. This review discusses white matter changes, with focus on oligodendrocyte lineage cells and their ability to produce and maintain myelin to support normal brain homoeostasis. Improved understanding of intrinsic cellular changes, general senescence mechanisms, intercellular interactions and alterations in extracellular environment which occur with aging and impact oligodendrocyte cells is paramount. This may lead to strategies to support oligodendrocytes in aging, for example by supporting myelin synthesis, protecting against oxidative stress and promoting the rejuvenation of the intrinsic regenerative potential of progenitor cells. Ultimately, this will enable the protection of white matter integrity thus protecting cognitive function into the later years of life.

28 citations

Journal ArticleDOI
TL;DR: Despite total brain zinc content is unchanged in the brain of aged animals, with respect to the young/adult, the activity of some zinc dependent enzymes is impaired and large amount of zinc has been found in the core of Alzheimer's disease senile plaques.
Abstract: Zinc maintains brain functions because involved in glutaminergic transmission, in antioxidant response and in conferring biological activity to brain enzymes and growth factors. Zinc turnover is mediated by Metallothioneins (MT) which regulate the intracellular free zinc ions [Zn](i). Alterations in zinc homeostasis are associated to various brain dysfunctions, including brain inflammatory status, but little is known about its implication in the aging brain and neurodegeneration. Literature data in experimental animals suggest that zinc dyshomeostasis may occur in aging associated to a decline in brain functions. One of the causes may be an altered homeostasis of MT and other zinc-binding proteins, such as alpha2 macroglobulin (A2M), which are of protection against stress and inflammation during young/adult age but turn into being harmful in aging. In fact, despite total brain zinc content is unchanged in the brain of aged animals, with respect to the young/adult, the activity of some zinc dependent enzymes is impaired and large amount of zinc has been found in the core of Alzheimer's disease senile plaques. The role played by MT and A2M is reported in ageing and Alzheimer's disease and on some polymorphisms of A2M and inflammatory genes (cytokines and their receptors) because some of them may be affected by zinc, via MT homeostasis.

28 citations

Journal ArticleDOI
TL;DR: The utility of a novel unsupervised machine learning technique – Correlation Explanation (CorEx) is shown to discover how individual measures from structural brain imaging, genetics, plasma, and CSF markers can jointly provide information on risk for Alzheimer’s disease.
Abstract: Brain aging is a multifaceted process that remains poorly understood. Despite significant advances in technology, progress towards identifying reliable risk factors for suboptimal brain health requires realistically complex analytic methods to explain relationships between genetics, biology, and environment. Here we show the utility of a novel unsupervised machine learning technique - Correlation Explanation (CorEx) - to discover how individual measures from structural brain imaging, genetics, plasma, and CSF markers can jointly provide information on risk for Alzheimer’s disease (AD). We examined 829 participants (Mage: 75.3 ± 6.9 years; 350 women and 479 men) from the Alzheimer’s Disease Neuroimaging Initiative database to identify multivariate predictors of cognitive decline and brain atrophy over a one-year period. Our sample included 231 cognitively normal individuals, 397 with mild cognitive impairment (MCI), and 201 with AD as their baseline diagnosis. Analyses revealed latent factors based on data-driven combinations of plasma markers and brain metrics, that were aligned with established biological pathways in AD. These factors were able to improve disease prediction along the trajectory from normal cognition and MCI to AD, with an area under the receiver operating curve of up to 99%, and prediction accuracy of up to 89.9% on independent “held out” testing data. Further, the most important latent factors that predicted AD consisted of a novel set of variables that are essential for cardiovascular, immune, and bioenergetic functions. Collectively, these results demonstrate the strength of unsupervised network measures in the detection and prediction of AD.

28 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202328
202256
202179
202072
201978
201872