Epigenetic signature of human immune aging in the GESTALT study
- National Institute on Aging, United States
Abstract
Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood borne immune cell types (naïve B, naïve CD4+ and CD8+ T cells, granulocytes, monocytes and NK cells) collected from healthy individuals interspersed over a wide age range. Of the thousands of age-associated sites, only 350 sites were differentially methylated in the same direction in all cell types and validated in an independent longitudinal cohort. Genes close to age-associated hypomethylated sites were enriched for collagen biosynthesis and complement cascade pathways, while genes close to hypermethylated sites mapped to neuronal pathways. In-silico analyses showed that in most cell types, the age-associated hypo- and hypermethylated sites were enriched for ARNT (HIF1β) and REST transcription factor motifs respectively, which are both master regulators of hypoxia response. To conclude, despite spatial heterogeneity, there is a commonality in the putative regulatory role with respect to transcription factor motifs and histone modifications at and around these sites. These features suggest that DNA methylation changes in healthy aging may be adaptive responses to fluctuations of oxygen availability.
Data availability
DNA methylation EPIC 850k data are available at GEO under accession number GSE184269
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InChianti Studyhttps://academic.oup.com/biomedgerontology/article/71/8/1029/2465635?login=false#82515120.
Article and author information
Author details
Ceereena Ubaida-Mohien
Funding
No external funding was received for this work.
Reviewing Editor
- Gabrielle T Belz, University of Queensland, Australia
Ethics
Human subjects: GESTALT study was approved by the institutional review board of the National Institutes of Health. Informed consent as well as the consent to publish the data collected was obtained from every participant in the study. Since the study of gene expression and epigenetic regulation are essential aims of GESTALT, all participants were required to consent to DNA/RNA testing and storage at all visits in order to participate in the study. the GESTALT IRB approval number is 15-AG-0063.
Version history
- Received: January 12, 2023
- Preprint posted: January 23, 2023 (view preprint)
- Accepted: August 16, 2023
- Accepted Manuscript published: August 17, 2023 (version 1)
- Version of Record published: September 18, 2023 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Epigenetic signature of human immune aging in the GESTALT study
eLife 12:e86136.
https://doi.org/10.7554/eLife.86136
Further reading
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