Hippocampal and cortical tissue-specific epigenetic clocks indicate an increased epigenetic age in a mouse model for Alzheimer’s disease

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Hippocampal and cortical tissue-specific epigenetic clocks indicate an increased epigenetic age in a mouse model for Alzheimer’s disease. / Coninx, Emma; Chew, Yap Ching; Yang, Xiaojing; Guo, Wei; Coolkens, Amelie; Baatout, Sarah; Moons, Lieve; Verslegers, Mieke; Quintens, Roel.

In: Aging, Vol. 12, No. 20, 104056, 10.2020, p. 20817-20834.

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@article{2272e6fb84214ad28803c9d53360ffdd,
title = "Hippocampal and cortical tissue-specific epigenetic clocks indicate an increased epigenetic age in a mouse model for Alzheimer’s disease",
abstract = "Epigenetic clocks are based on age-associated changes in DNA methylation of CpG-sites, which can accurately measure chronological age in different species. Recently, several studies have indicated that the difference between chronological and epigenetic age, defined as the age acceleration, could reflect biological age indicating functional decline and age-associated diseases. In humans, an epigenetic clock associated Alzheimer’s disease (AD) pathology with an acceleration of the epigenetic age. In this study, we developed and validated two mouse brain region-specific epigenetic clocks from the C57BL/6J hippocampus and cerebral cortex. Both clocks, which could successfully estimate chronological age, were further validated in a widely used mouse model for AD, the triple transgenic AD (3xTg-AD) mouse. We observed an epigenetic age acceleration indicating an increased biological age for the 3xTg-AD mice compared to non-pathological C57BL/6J mice, which was more pronounced in the cortex as compared to the hippocampus. Genomic region enrichment analysis revealed that age-dependent CpGs were enriched in genes related to developmental, aging-related, neuronal and neurodegenerative functions. Due to the limited access of human brain tissues, these epigenetic clocks specific for mouse cortex and hippocampus might be important in further unravelling the role of epigenetic mechanisms underlying AD pathology or brain aging in general.",
keywords = "Epigenetic clock, Alzheimer's disease, Epigenetic age, Brain aging",
author = "Emma Coninx and Chew, {Yap Ching} and Xiaojing Yang and Wei Guo and Amelie Coolkens and Sarah Baatout and Lieve Moons and Mieke Verslegers and Roel Quintens",
note = "Score=10",
year = "2020",
month = "10",
doi = "10.18632/aging.104056",
language = "English",
volume = "12",
pages = "20817--20834",
journal = "Aging",
issn = "1945-4589",
publisher = "Impact Journals",
number = "20",

}

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TY - JOUR

T1 - Hippocampal and cortical tissue-specific epigenetic clocks indicate an increased epigenetic age in a mouse model for Alzheimer’s disease

AU - Coninx, Emma

AU - Chew, Yap Ching

AU - Yang, Xiaojing

AU - Guo, Wei

AU - Coolkens, Amelie

AU - Baatout, Sarah

AU - Moons, Lieve

AU - Verslegers, Mieke

AU - Quintens, Roel

N1 - Score=10

PY - 2020/10

Y1 - 2020/10

N2 - Epigenetic clocks are based on age-associated changes in DNA methylation of CpG-sites, which can accurately measure chronological age in different species. Recently, several studies have indicated that the difference between chronological and epigenetic age, defined as the age acceleration, could reflect biological age indicating functional decline and age-associated diseases. In humans, an epigenetic clock associated Alzheimer’s disease (AD) pathology with an acceleration of the epigenetic age. In this study, we developed and validated two mouse brain region-specific epigenetic clocks from the C57BL/6J hippocampus and cerebral cortex. Both clocks, which could successfully estimate chronological age, were further validated in a widely used mouse model for AD, the triple transgenic AD (3xTg-AD) mouse. We observed an epigenetic age acceleration indicating an increased biological age for the 3xTg-AD mice compared to non-pathological C57BL/6J mice, which was more pronounced in the cortex as compared to the hippocampus. Genomic region enrichment analysis revealed that age-dependent CpGs were enriched in genes related to developmental, aging-related, neuronal and neurodegenerative functions. Due to the limited access of human brain tissues, these epigenetic clocks specific for mouse cortex and hippocampus might be important in further unravelling the role of epigenetic mechanisms underlying AD pathology or brain aging in general.

AB - Epigenetic clocks are based on age-associated changes in DNA methylation of CpG-sites, which can accurately measure chronological age in different species. Recently, several studies have indicated that the difference between chronological and epigenetic age, defined as the age acceleration, could reflect biological age indicating functional decline and age-associated diseases. In humans, an epigenetic clock associated Alzheimer’s disease (AD) pathology with an acceleration of the epigenetic age. In this study, we developed and validated two mouse brain region-specific epigenetic clocks from the C57BL/6J hippocampus and cerebral cortex. Both clocks, which could successfully estimate chronological age, were further validated in a widely used mouse model for AD, the triple transgenic AD (3xTg-AD) mouse. We observed an epigenetic age acceleration indicating an increased biological age for the 3xTg-AD mice compared to non-pathological C57BL/6J mice, which was more pronounced in the cortex as compared to the hippocampus. Genomic region enrichment analysis revealed that age-dependent CpGs were enriched in genes related to developmental, aging-related, neuronal and neurodegenerative functions. Due to the limited access of human brain tissues, these epigenetic clocks specific for mouse cortex and hippocampus might be important in further unravelling the role of epigenetic mechanisms underlying AD pathology or brain aging in general.

KW - Epigenetic clock

KW - Alzheimer's disease

KW - Epigenetic age

KW - Brain aging

UR - https://ecm.sckcen.be/OTCS/llisapi.dll/overview/42248804

U2 - 10.18632/aging.104056

DO - 10.18632/aging.104056

M3 - Article

VL - 12

SP - 20817

EP - 20834

JO - Aging

JF - Aging

SN - 1945-4589

IS - 20

M1 - 104056

ER -

ID: 7038436