Accelerated aging with HIV begins at the time of initial HIV infection

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

doi:10.1016/j.isci.2022.104488

Accelerated aging with HIV begins at the time of initial HIV infection

iScience. 2022 Jun 30;25(7):104488. doi: 10.1016/j.isci.2022.104488. eCollection 2022 Jul 15.

Authors

Elizabeth Crabb Breen¹, Mary E Sehl², Roger Shih², Peter Langfelder^{3

4}, Ruibin Wang⁵, Steve Horvath^{6

7}, Jay H Bream⁸, Priya Duggal⁵, Jeremy Martinson⁹, Steven M Wolinsky¹⁰, Otoniel Martínez-Maza¹¹, Christina M Ramirez¹², Beth D Jamieson²

Affiliations

¹ Cousins Center for Psychoneuroimmunology, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.
² Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.
³ Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA 21205, USA.
⁶ Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁷ Altos Labs, San Diego, CA 92121, USA.
⁸ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Graduate Program in Immunology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
⁹ Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
¹⁰ Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹¹ Departments of Obstetrics & Gynecology and Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.
¹² Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA.

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.

Keywords: Epigenetics; Human physiology; Immunology; Virology.

Abstract

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