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Aging
Article . 2017 . Peer-reviewed
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Aging
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Aging
Article . 2018
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Accelerated epigenetic aging in Werner syndrome

Authors: Maierhofer, Anna; Flunkert, Julia; Oshima, Junko; Martin, George M; Haaf, Thomas; Horvath, Steve;

Accelerated epigenetic aging in Werner syndrome

Abstract

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown.

Country
United States
Keywords

Adult, Male, Aging, 610, Clinical sciences, CD8-Positive T-Lymphocytes, Epigenesis, Genetic, Rare Diseases, Genetic, Genetics, 80 and over, 2.1 Biological and endogenous factors, Humans, Lymphocyte Count, Aetiology, Premature, Aged, Werner syndrome, Aged, 80 and over, Sex Characteristics, DNA methylation, Blood Cells, epigenetics, progeria, Aging, Premature, Biological Sciences, DNA Methylation, Middle Aged, Blood Cell Count, Biochemistry and cell biology, Female, Werner Syndrome, epigenetic clock, Biomarkers, Epigenesis, Research Paper, DNA Damage

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
149
Top 1%
Top 10%
Top 1%
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