Increased Rate of Epigenetic Aging in Men Living With HIV Prior to Treatment

Mary E Sehl; Elizabeth Crabb Breen; Roger Shih; Larry Chen; Ruibin Wang; Steve Horvath; Jay H Bream; Priya Duggal; Jeremy Martinson; Steven M Wolinsky; Otoniel Martinez-Maza; Christina M Ramirez; Beth D Jamieson

doi:10.3389/fgene.2021.796547

Increased Rate of Epigenetic Aging in Men Living With HIV Prior to Treatment

Front Genet. 2022 Feb 28:12:796547. doi: 10.3389/fgene.2021.796547. eCollection 2021.

Authors

Affiliations

¹ Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States.
² Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States.
³ UCLA Computational and Systems Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, United States.
⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
⁵ Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Immunology Training Program, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁷ Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.
⁸ Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
⁹ Departments of Obstetrics and Gynecology and Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States.
¹⁰ Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Background: Epigenetic aging is accelerated in tissues of persons living with HIV (PLWH) and may underlie the early onset of age-related illnesses. This study examines the rate-of-change in epigenetic age in PLWH following HIV infection but before HAART, using archived longitudinal samples from the Multicenter AIDS Cohort Study. Methods: DNA was isolated from cryopreserved peripheral blood mononuclear cells from 101 men living with HIV, with baseline visit <2.5 years after HIV seroconversion (Visit 1) and follow-up visit <1.5 years before the initiation of HAART (Visit 2), and 100 HIV-uninfected men matched on age and visits with comparable time intervals. DNA methylation (DNAm) age was estimated for five clocks (Pan-tissue, Extrinsic, Phenotypic, Grim, and Skin & Blood age), and a DNAm-based estimate of telomere length (DNAmTL). Multivariate linear regression models were used to examine baseline factors associated with rate-of-aging, defined as (DNAm age visit 2-DNAm age visit 1)/(age visit 2-age visit 1). Results: Epigenetic age increased approximately twice as fast in PLWH as uninfected controls (Pan-tissue, Extrinsic, and Phenotypic clocks). Shortening of DNAmTL was nearly 3-fold faster in PLWH than controls. Faster rate-of-aging was associated with HIV status (Pan-Tissue, Extrinsic, Phenotypic, and DNAmTL), white race (Extrinsic, DNAmTL), higher cumulative HIV viral load (Grim), and lower baseline DNAm age (Phenotypic, Skin & Blood). Conclusion: Epigenetic rates-of-aging were significantly faster for untreated PLWH. Our findings expand on the important impact of HIV infection on biologic aging, both in elevating epigenetic age and increasing the rate-of-aging in the years following infection.

Keywords: DNA methylation; HIV; aging; epigenetic clock; telomeres.

Abstract

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