Frontiers in Genetics (Feb 2022)

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,
  • Otoniel Martinez-Maza,
  • Christina M. Ramirez,
  • Beth D. Jamieson

DOI
https://doi.org/10.3389/fgene.2021.796547
Journal volume & issue
Vol. 12

Abstract

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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.

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