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. 2017 Feb 23;9(3):687-705.
doi: 10.18632/aging.101184.

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion

Janice M Leung  1   2   3 , Nick Fishbane  1 , Meaghan Jones  4 , Alexander Morin  4 , Stella Xu  1 , Joseph Cy Liu  1 , Julie MacIsaac  4 , M-J Milloy  3 , Kanna Hayashi  3   5 , Julio Montaner  3 , Steve Horvath  6 , Michael Kobor  4 , Don D Sin  1   2 , P Richard Harrigan  4 , S F Paul Man  1   2
Affiliations

Longitudinal study of surrogate aging measures during human immunodeficiency virus seroconversion

Janice M Leung et al. Aging (Albany NY). .

Abstract

Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to PCBP2 and CSRNP1 were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.

Keywords: HIV; aging; methylation; seroconversion; telomere.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A)The correlation between absolute telomere length and age is shown, demonstrating that shorter telomere lengths are observed with older age (p=0.017, Pearson's rho=-0.268). (B) Absolute telomere length measurements are shown for T1, T2, and T3. By paired t-test, there was a significant decrease in telomere length between T1 and T2 (p=0.045), but no significant change between T2 and T3 (p=0.244).
Figure 2
Figure 2
(A) The correlation between DNA methylation age and chronologic age from all subjects inclusive of all time points is shown, demonstrating a high correlation between the two measures (p<2.2e-16, Pearson's rho=0.896). (B) The age acceleration residual (greater positivity on this scale represents more advanced methylation age in relation to chronologic age) increases over the time course of HIV infection (p=0.035, Pearson's rho=0.236). Black dots represent HIV-negative time points (T1) while red dots represent HIV-positive time points (T2 and T3).
Figure 3
Figure 3
A volcano plot demonstrating differentially methylated CpG sites in T2 vs. T1. Two CpG sites (corresponding to PCBP2 and CSRNP1) had q-values <0.05, while four additional CpG sites (corresponding to PDE7a, FAM46C, PNKD:TMBIM1, and an unknown gene) had q-values <0.20.
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