Epigenetic signature of human immune aging in the GESTALT study

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...

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Vydáno v:eLife Ročník 12
Hlavní autoři: Roy, Roshni, Kuo, Pei-Lun, Candia, Julián, Sarantopoulou, Dimitra, Ubaida-Mohien, Ceereena, Hernandez, Dena, Kaileh, Mary, Arepalli, Sampath, Singh, Amit, Bektas, Arsun, Kim, Jaekwan, Moore, Ann Z, Tanaka, Toshiko, McKelvey, Julia, Zukley, Linda, Nguyen, Cuong, Wallace, Tonya, Dunn, Christopher, Wood, William, Piao, Yulan, Coletta, Christopher, De, Supriyo, Sen, Jyoti, Weng, Nan-ping, Sen, Ranjan, Ferrucci, Luigi
Médium: Journal Article
Jazyk:angličtina
Vydáno: Cambridge eLife Science Publications, Ltd 17.08.2023
eLife Sciences Publications Ltd
eLife Sciences Publications, Ltd
Témata:
Age
Aging
Biotechnology industry
Blood
CD4 antigen
CD8 antigen
Cells
Complement system
DNA methylation
Epigenetic inheritance
Epigenetics
Gene regulation
Genetics and Genomics
healthy aging
Histones
Hypotheses
Hypoxia
immune cells
Immunology and Inflammation
Killer cells
Leukocytes (granulocytic)
Lymphocytes
Lymphocytes T
Methylation
Monocytes
Physiological aspects
Principal components analysis
Spatial heterogeneity
T cells
Canada
United States
ISSN:2050-084X, 2050-084X
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Shrnutí: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 (naive B, naive 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 (TF) 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 TF 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.
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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.86136