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

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.

SUBMITTER: Breen EC

PROVIDER: S-EPMC9308149 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Breen Elizabeth Crabb EC Sehl Mary E ME Shih Roger R Langfelder Peter P Wang Ruibin R Horvath Steve S Bream Jay H JH Duggal Priya P Martinson Jeremy J Wolinsky Steven M SM Martínez-Maza Otoniel O Ramirez Christina M CM Jamieson Beth D BD

iScience 20220630 7

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 telo ...[more]

PMID: 35880029

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Project description:Experiencing adversity in childhood and adolescence, including stressful life events (SLEs), may accelerate the pace of development, leading to adverse mental and physical health. However, most research on adverse early experiences and biological aging (BA) in youths relies on cross-sectional designs. In 171 youths followed for approximately 2 years, we examined if SLEs over follow-up predicted rate of change in two BA metrics: epigenetic age and Tanner stage. We also investigated if rate of change in BA was associated with changes in depressive symptoms over time. Youths aged 8-16 years at baseline self-reported Tanner stage and depressive symptoms at baseline and follow-up and provided saliva samples for DNA at both assessments. Horvath epigenetic age estimates were derived from DNA methylation data measured with the Illumina EPIC array. At follow-up, contextual threat interviews were administered to youths and caregivers to assess youths' experiences of past-year SLEs. Interviews were objectively coded by an independent rating team to generate a SLE impact score, reflecting the severity of all SLEs occurring over the prior year. Rate of change in BA metrics was operationalized as change in epigenetic age or Tanner stage as a function of time between assessments. Higher objective SLE impact scores over follow-up were related to a greater rate of change in epigenetic age (β = 0.21, p = .043). Additionally, among youths with lower-but not higher-Tanner stage at baseline, there was a positive association of SLE impact scores with rate of change in Tanner stage (Baseline Tanner Stage × SLE Impact Score interaction: β = - 0.21, p = .011). A greater rate of change in epigenetic age was also associated with higher depressive symptom levels at follow-up, adjusting for baseline symptoms (β = 0.15, p = .043). Associations with epigenetic age were similar, although slightly attenuated, when adjusting for epithelial (buccal) cell proportions. Whereas much research in youths has focused on severe experiences of early adversity, we demonstrate that more commonly experienced SLEs during adolescence may also contribute to accelerated BA. Further research is needed to understand the long-term consequences of changes in BA metrics for health.

Dataset Information

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

Publications

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

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