Age-related variations in the methylome associated with gene expression in human monocytes and T cells

Lindsay M. Reynolds; Jackson R. Taylor; Jingzhong Ding; Kurt Lohman; Craig Johnson; David Siscovick; Gregory Burke; Wendy Post; Steven Shea; David R. Jacobs; Hendrik Stunnenberg; Stephen B. Kritchevsky; Ina Hoeschele; Charles E. McCall; David M. Herrington; Russell P. Tracy; Yongmei Liu

doi:10.1038/ncomms6366

Age-related variations in the methylome associated with gene expression in human monocytes and T cells

Lindsay M. Reynolds, Jackson R. Taylor, Jingzhong Ding, Kurt Lohman, Craig Johnson, David Siscovick, Gregory Burke, Wendy Post, Steven Shea, David R. Jacobs, Hendrik Stunnenberg, Stephen B. Kritchevsky, Ina Hoeschele, Charles E. McCall, David M. Herrington, Russell P. Tracy, Yongmei Liu

Epidemiology & Community Health

Research output: Contribution to journal › Article › peer-review

135 Scopus citations

Abstract

Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.

Original language	English (US)
Article number	5366
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6366
State	Published - 2014

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Reynolds, L. M., Taylor, J. R., Ding, J., Lohman, K., Johnson, C., Siscovick, D., Burke, G., Post, W., Shea, S., Jacobs, D. R., Stunnenberg, H., Kritchevsky, S. B., Hoeschele, I., McCall, C. E., Herrington, D. M., Tracy, R. P., & Liu, Y. (2014). Age-related variations in the methylome associated with gene expression in human monocytes and T cells. Nature communications, 5, Article 5366. https://doi.org/10.1038/ncomms6366

Reynolds, LM, Taylor, JR, Ding, J, Lohman, K, Johnson, C, Siscovick, D, Burke, G, Post, W, Shea, S, Jacobs, DR, Stunnenberg, H, Kritchevsky, SB, Hoeschele, I, McCall, CE, Herrington, DM, Tracy, RP & Liu, Y 2014, 'Age-related variations in the methylome associated with gene expression in human monocytes and T cells', Nature communications, vol. 5, 5366. https://doi.org/10.1038/ncomms6366

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abstract = "Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.",

author = "Reynolds, {Lindsay M.} and Taylor, {Jackson R.} and Jingzhong Ding and Kurt Lohman and Craig Johnson and David Siscovick and Gregory Burke and Wendy Post and Steven Shea and Jacobs, {David R.} and Hendrik Stunnenberg and Kritchevsky, {Stephen B.} and Ina Hoeschele and McCall, {Charles E.} and Herrington, {David M.} and Tracy, {Russell P.} and Yongmei Liu",

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AU - Siscovick, David

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AU - Post, Wendy

AU - Shea, Steven

AU - Jacobs, David R.

AU - Stunnenberg, Hendrik

AU - Kritchevsky, Stephen B.

AU - Hoeschele, Ina

AU - McCall, Charles E.

AU - Herrington, David M.

AU - Tracy, Russell P.

AU - Liu, Yongmei

PY - 2014

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N2 - Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.

AB - Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process.

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Age-related variations in the methylome associated with gene expression in human monocytes and T cells

Abstract

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