Abstract
Living with HIV infection is associated with early onset of aging-related chronic conditions, sometimes described as accelerated aging. Epigenetic DNA methylation patterns can evaluate acceleration of biological age relative to chronological age. The impact of initial HIV infection on five epigenetic measures of aging was examined before and approximately 3 years after HIV infection in the same individuals (n=102). Significant epigenetic age acceleration (median 1.9–4.8 years) and estimated telomere length shortening (all p≤ 0.001) were observed from pre-to post-HIV infection, and remained significant in three epigenetic measures after controlling for T cell changes. No acceleration was seen in age- and time interval-matched HIV-uninfected controls. Changes in genome-wide co-methylation clusters were also significantly associated with initial HIV infection (p≤ 2.0 × 10−4). These longitudinal observations clearly demonstrate an early and substantial impact of HIV infection on the epigenetic aging process, and suggest a role for HIV itself in the earlier onset of clinical aging.
| Original language | English (US) |
|---|---|
| Article number | 104488 |
| Journal | iScience |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 15 2022 |
Funding
The authors gratefully acknowledge the contributions of the study participants and dedication of the staff at the MWCCS sites. We also thank Diane Gu, Lillia Zograbya, and Marianne Chow for data management and technical assistance. The methylation data were produced with the assistance of the Neuroscience Genomics Core at UCLA. Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility supported by National Institutes of Health (NIH) awards P30 CA016042 and 5P30 AI028697 , and by the JCCC , AIDS Institute , David Geffen School of Medicine , Chancellor's Office, and Vice Chancellor's Office of Research at UCLA . The graphical abstract was created with BioRender.com . This work was supported by grants R01 AG052340 and R01 AG030327 from the NIH National Institute on Aging to B.D. Jamieson who is also supported by U01-HL146333 , and by the Susan G. Komen Career Catalyst Award CCR16380478 to M.E. Sehl. Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS), now the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the NIH . Contributing MWCCS sites (Principal Investigators): Baltimore CRS (T. Brown, J. Margolick), U01-HL146201 ; Data Analysis and Coordination Center (G. D’Souza, S. Gange, E. Golub), U01-HL146193 ; Chicago-Northwestern CRS (S. Wolinsky), U01-HL146240; Los Angeles CRS (R. Detels, M. Mimiaga), U01-HL146333 ; Pittsburgh CRS (J. Martinson, C. Rinaldo), U01-HL146208 . The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from other Institutes, and in coordination and alignment with the research priorities of the NIH Office of AIDS Research (OAR). Contributing MWCCS sites data collection is also supported by UL1-TR003098 ( JHUICTR ), UL1-TR001881 ( UCLA CTSI ). The authors gratefully acknowledge the contributions of the study participants and dedication of the staff at the MWCCS sites. We also thank Diane Gu, Lillia Zograbya, and Marianne Chow for data management and technical assistance. The methylation data were produced with the assistance of the Neuroscience Genomics Core at UCLA. Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility supported by National Institutes of Health (NIH) awards P30 CA016042 and 5P30 AI028697, and by the JCCC, AIDS Institute, David Geffen School of Medicine, Chancellor's Office, and Vice Chancellor's Office of Research at UCLA. The graphical abstract was created with BioRender.com. This work was supported by grants R01 AG052340 and R01 AG030327 from the NIH National Institute on Aging to B.D. Jamieson who is also supported by U01-HL146333, and by the Susan G. Komen Career Catalyst Award CCR16380478 to M.E. Sehl. Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS), now the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the NIH. Contributing MWCCS sites (Principal Investigators):Baltimore CRS (T. Brown, J. Margolick), U01-HL146201; Data Analysis and Coordination Center (G. D'Souza, S. Gange, E. Golub), U01-HL146193; Chicago-Northwestern CRS (S. Wolinsky), U01-HL146240;Los Angeles CRS (R. Detels, M. Mimiaga), U01-HL146333;Pittsburgh CRS (J. Martinson, C. Rinaldo), U01-HL146208. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from other Institutes, and in coordination and alignment with the research priorities of the NIH Office of AIDS Research (OAR). Contributing MWCCS sites data collection is also supported by UL1-TR003098 (JHUICTR), UL1-TR001881(UCLA CTSI). Conceptualization, B.D.J.; Methodology, E.C.B. R.W. C.M.R. and B.D.J.; Formal Analysis, M.E.S. R.S. P.L. and C.M.R.; Investigation, E.C.B. and R.S.; Resources, S.H. J.H.B. P.D. J.M. S.M.W. O.M-M.; Data Curation, R.S. Writing – Original Draft, E.C.B. and M.E.S.; Writing – Review & Editing, E.C.B. M.E.S. R.S. R.W. S.H. P.L. J.H.B. P.D. J.M. S.M.W. O.M-M. C.M.R. and B.D.J.; Visualization, E.C.B. and R.S.; Supervision, S.H. and B.D.J.; Funding Acquisition, B.D.J. and M.E.S. Peter Langfelder is a paid consultant for The Bioinformatics CRO, Inc and Quantigic Genomics, LLC. Steve Horvath is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. These patents list SH as inventor.
Keywords
- Epigenetics
- Human physiology
- Immunology
- Virology
ASJC Scopus subject areas
- General
