Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy

Chen Xi Yang; Emma Schon; Ma'en Obeidat; Michael S. Kobor; Lisa McEwen; Julie MacIsaac; David Lin; Richard M. Novak; Fleur Hudson; Hartwig Klinker; Nila Dharan; Steve Horvath; Jean Bourbeau; Wan Tan; Don D. Sin; S. F.Paul Man; Ken Kunisaki; Janice M. Leung

doi:10.1093/infdis/jiaa599

Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy

Chen Xi Yang, Emma Schon, Ma'en Obeidat, Michael S. Kobor, Lisa McEwen, Julie MacIsaac, David Lin, Richard M. Novak, Fleur Hudson, Hartwig Klinker, Nila Dharan, Steve Horvath, Jean Bourbeau, Wan Tan, Don D. Sin, S. F.Paul Man, Ken Kunisaki, Janice M. Leung

Medicine - Veteran's Administration Medical Center

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

20 Scopus citations

Abstract

BACKGROUND: Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART).

METHODS: A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock.

RESULTS: There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of <0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration.

CONCLUSIONS: PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.

Original language	English (US)
Pages (from-to)	1681-1689
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	223
Issue number	10
DOIs	https://doi.org/10.1093/infdis/jiaa599
State	Published - May 15 2021

Bibliographical note

Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Keywords

HIV
aging
epigenetics
methylation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Yang, C. X., Schon, E., Obeidat, M., Kobor, M. S., McEwen, L., MacIsaac, J., Lin, D., Novak, R. M., Hudson, F., Klinker, H., Dharan, N., Horvath, S., Bourbeau, J., Tan, W., Sin, D. D., Man, S. F. P., Kunisaki, K., & Leung, J. M. (2021). Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy. Journal of Infectious Diseases, 223(10), 1681-1689. https://doi.org/10.1093/infdis/jiaa599

Yang, CX, Schon, E, Obeidat, M, Kobor, MS, McEwen, L, MacIsaac, J, Lin, D, Novak, RM, Hudson, F, Klinker, H, Dharan, N, Horvath, S, Bourbeau, J, Tan, W, Sin, DD, Man, SFP, Kunisaki, K & Leung, JM 2021, 'Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy', Journal of Infectious Diseases, vol. 223, no. 10, pp. 1681-1689. https://doi.org/10.1093/infdis/jiaa599

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abstract = "BACKGROUND: Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART).METHODS: A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock.RESULTS: There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of <0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration.CONCLUSIONS: PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.",

keywords = "HIV, aging, epigenetics, methylation",

author = "Yang, {Chen Xi} and Emma Schon and Ma'en Obeidat and Kobor, {Michael S.} and Lisa McEwen and Julie MacIsaac and David Lin and Novak, {Richard M.} and Fleur Hudson and Hartwig Klinker and Nila Dharan and Steve Horvath and Jean Bourbeau and Wan Tan and Sin, {Don D.} and Man, {S. F.Paul} and Ken Kunisaki and Leung, {Janice M.}",

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doi = "10.1093/infdis/jiaa599",

language = "English (US)",

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T1 - Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy

AU - Yang, Chen Xi

AU - Schon, Emma

AU - Obeidat, Ma'en

AU - Kobor, Michael S.

AU - McEwen, Lisa

AU - MacIsaac, Julie

AU - Lin, David

AU - Novak, Richard M.

AU - Hudson, Fleur

AU - Klinker, Hartwig

AU - Dharan, Nila

AU - Horvath, Steve

AU - Bourbeau, Jean

AU - Tan, Wan

AU - Sin, Don D.

AU - Man, S. F.Paul

AU - Kunisaki, Ken

AU - Leung, Janice M.

PY - 2021/5/15

Y1 - 2021/5/15

N2 - BACKGROUND: Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART).METHODS: A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock.RESULTS: There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of <0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration.CONCLUSIONS: PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.

AB - BACKGROUND: Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART).METHODS: A total of 378 ART-naive PLWH who had CD4 T-cell counts >500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock.RESULTS: There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of <0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration.CONCLUSIONS: PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.

KW - HIV

KW - aging

KW - epigenetics

KW - methylation

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AN - SCOPUS:85102415760

SN - 0022-1899

VL - 223

SP - 1681

EP - 1689

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 10

ER -

Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy

Abstract

Bibliographical note

Keywords

UN SDGs

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