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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number796547
JournalFrontiers in Genetics
Volume12
DOIs
StatePublished - Feb 28 2022

Keywords

  • DNA methylation
  • HIV
  • aging
  • epigenetic clock
  • telomeres

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Molecular Medicine

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