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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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
StatePublished - Feb 28 2022


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

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)


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