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The epigenetics of aging and neurodegeneration
Open accessAbstract
Epigenetics is a quickly growing field encompassing mechanisms regulating gene expression that do not involve changes in the genotype. Epigenetics is of increasing relevance to neuroscience, with epigenetic mechanisms being implicated in brain development and neuronal differentiation, as well as in more dynamic processes related to cognition. Epigenetic regulation covers multiple levels of gene expression; from direct modifications of the DNA and histone tails, regulating the level of transcription, to interactions with messenger RNAs, regulating the level of translation. Importantly, epigenetic dysregulation currently garners much attention as a pivotal player in aging and age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, where it may mediate interactions between genetic and environmental risk factors, or directly interact with disease-specific pathological factors. We review current knowledge about the major epigenetic mechanisms, including DNA methylation and DNA demethylation, chromatin remodeling and non-coding RNAs, as well as the involvement of these mechanisms in normal aging and in the pathophysiology of the most common neurodegenerative diseases. Additionally, we examine the current state of epigenetics-based therapeutic strategies for these diseases, which either aim to restore the epigenetic homeostasis or skew it to a favorable direction to counter disease pathology. Finally, methodological challenges of epigenetic investigations and future perspectives are discussed.
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“Furthermore, the cellular heterogeneity of the AD brain presents significant analytical hurdles. Advanced computational deconvolution techniques or experimental methods such as fluorescence-activated cell sorting (FACS) are often required to resolve distinct cell populations, including neurons, astrocytes, and microglia127,157.”
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Metadata
- Authors
- Lardenoije, R., Iatrou, A., Kenis, G., Kompotis, K., Steinbusch, H. W. M., Mastroeni, D., Coleman, P., Lemere, C. A., Hof, P. R., van den Hove, D. L. A., & Rutten, B. P. F.
- Affiliations
- Maastricht University (NL)
- University of Lausanne (CH)
- Banner Sun Health Research Institute (US)
- Brigham and Women's Hospital (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Rutten, Bart P.F.
- ORCID
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 131
- Pages
- 21-64
- ISSN
- 0301-0082 (ISSN-L)
- PMC
- PMC6477921
- OpenAlex
- W648684004
- Cited by
- 381
- References
- 770
- Citations by year
- 2026: 12 · 2025: 29 · 2024: 28 · 2023: 28 · 2022: 32 · 2021: 47 · 2020: 30 · 2019: 42 · 2018: 39 · 2017: 43 · 2016: 38 · 2015: 11
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- Internationale Stichting Alzheimer Onderzoek (07551, 11532, 09552, 13515)
- Netherlands Organization for Scientific Research (916.11.086)
- National Institutes of Health (P50 AG005138)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- epigenetics, aging, neurodegeneration, DNA methylation, DNA demethylation, chromatin remodeling, non-coding RNA, Alzheimer's disease, Parkinson's disease, Huntington's disease, epigenetic therapy, gene expression regulation, histone modifications
- MeSH terms
- Aging, Animals, Humans, DNA Methylation, Neurodegenerative Diseases, Genetic Predisposition to Disease, RNA, Untranslated, Epigenesis, Genetic
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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