Mapping Genetics and Epigenetics to Explore the Pathways beyond the Correlated Ageing Phenotype

Ghanemi, Abdelaziz; Yoshioka, Mayumi; St‐Amand, Jonny

doi:10.3390/genes13112169

Cited by 2 publications

(1 citation statement)

References 76 publications

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“…Increasing evidence indicates that Wnt signaling regulates multiple aspects of adult hippocampal neurogenesis 65 as well as neural function and synaptic connectivity 66 and downregulation of Wnt signaling could be involved in the cognitive decline associated with aging and Alzheimer’s disease 67 . Together, our transcriptome analysis aligns with previous studies 68,36 , suggesting a consistent and generalized pattern of gene expression changes associated with aging.…”

Section: Discussionsupporting

confidence: 88%

Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aging Brain

Mancino,

Seneviratne,

Mupo

et al. 2023

Preprint

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Epigenetic drift is a hallmark of aging that contributes to the irreversible decline in organismal fitness ultimately leading to aging-related diseases. Epigenetic modifications regulate the cellular memory of the epigenetic processes of genomic imprinting and X-chromosome inactivation to ensure monoallelic expression of imprinted and X-linked genes. Whether epigenetic drift affects maintenance of genomic imprinting and X-chromosome inactivation has not been comprehensively studied. Here, we investigate the allele-specific transcriptional and epigenetic signatures of the aging brain, by comparing juvenile and old hybrid mice obtained from C57BL/6J (BL6) & CAST/EiJ (CAST) reciprocal crosses, with an emphasis on the hippocampus (HCP). We confirm that the aged HCP shows an increase of DNA hydroxymethylation, a sign of epigenetic drift, and a typical aging transcriptional signature. Genomic imprinting was found to be largely unaffected with stable parent-of-origin-specific DNA methylation in HCP, but also other brain regions such as the cerebellum (CB), nucleus accumbens, hypothalamus and prefrontal cortex. Consistently, transcriptomics analysis confirmed unaltered imprinting expression in the aged HCP. An exception are three novel non-coding transcripts (B230209E15Rik,Ube2nlandA330076H08Rik) at the Prader-Willi syndrome/Angelman syndrome (PWS/AS) imprinted locus which lose strict monoallelic expression during aging. Like imprinting, X-chromosome inactivation was remarkably stable with no signs of aging-driven skewing or relaxation of monoallelic expression of X-linked genes. Our study provides a valuable resource for evaluating monoallelic expression in the aging brain and reveals that, despite epigenetic drift during aging, genomic imprinting and X-chromosome inactivation remain predominantly stable throughout the process of physiological aging in the mouse brain.

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Section: Discussionsupporting

confidence: 88%

Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aging Brain

Mancino,

Seneviratne,

Mupo

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Exploring the Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aged Brain

Eckersley-Maslin,

Teixeira da Rocha,

Mancino

et al. 2024

AgingBio

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Changes in the epigenetic landscape are a hallmark of aging that contributes to the irreversible decline in organismal fitness ultimately leading to aging-related diseases. Epigenetic modifications regulate the cellular memory of the epigenetic processes of genomic imprinting and X-chromosome inactivation (XCI) to ensure monoallelic expression of imprinted and X-linked genes. Whether aging-associated epigenetic changes affect the maintenance of genomic imprinting and XCI has not been comprehensively studied.Here, we investigate the allele-specific transcriptional and epigenetic signatures of the aging brain, by comparing juvenile and old hybrid mice obtained from C57BL/6J (BL6) and CAST/EiJ (CAST) reciprocal crosses, with an emphasis on the hippocampus (HCP). We confirmed that the aged HCP showed an expected increase in DNA hydroxymethylation and a typical aging transcriptional signature. Importantly, genomic imprinting was largely unaffected, with stable parent-of-origin-specific DNA methylation in multiple brain regions including the HCP, cerebellum, nucleus accumbens, hypothalamus, and prefrontal cortex. Consistently, allele-specific transcriptomic bulk analysis confirmed unaltered imprinting expression in the aged HCP. An exception was four novel non-coding transcripts (B230209E15Rik, Ube2nl, A330076H08Rik, and A230057D06Rik) at the Prader-Willi syndrome/Angelman syndrome imprinted locus, which lost strict monoallelic expression during aging. Similar to imprinting, XCI was remarkably stable with no signs of aging-driven skewing or relaxation of monoallelic expression of X-linked genes. Our study provides a valuable resource for evaluating monoallelic expression in the aging brain and reveals that, despite the known epigenetic changes occurring during aging, genomic imprinting and XCI remain predominantly stable throughout the process of physiological aging in the mouse brain.

show abstract

Mapping Genetics and Epigenetics to Explore the Pathways beyond the Correlated Ageing Phenotype

Cited by 2 publications

References 76 publications

Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aging Brain

Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aging Brain

Exploring the Stability of Genomic Imprinting and X-Chromosome Inactivation in the Aged Brain

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