与人类免疫缺陷病毒（HIV）感染的老年非裔美国人认知障碍相关的表观遗传衰老生物标志物。
Epigenetic Aging Biomarkers Associated With Cognitive Impairment in Older African American Adults With Human Immunodeficiency Virus (HIV).
机构信息
Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, USA.
Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA.
出版信息
Clin Infect Dis. 2021 Dec 6;73(11):1982-1991. doi: 10.1093/cid/ciab563.
BACKGROUND
Accelerated epigenetic aging using DNA methylation (DNAm)-based biomarkers has been reported in people with human immunodeficiency virus (HIV, PWH), but limited data are available among African Americans (AA), women, and older PWH.
METHODS
DNAm was measured using Illumina EPIC Arrays for 107 (69 PWH and 38 HIV-seronegative controls) AA adults ≥60 years in New York City. Six DNAm-based biomarkers of aging were estimated: (1) epigenetic age acceleration (EAA), (2) extrinsic epigenetic age acceleration (EEAA), (3) intrinsic epigenetic age acceleration (IEAA), (4) GrimAge, (5) PhenoAge, and (6) DNAm-estimated telomere length (DNAm-TL). The National Institutes of Health (NIH) Toolbox Cognition Battery (domains: executive function, attention, working memory, processing speed, and language) and Montreal Cognitive Assessment (MoCA) were administered. Participants were assessed for frailty by the Fried criteria.
RESULTS
The PWH and control groups did not differ by sex, chronological age, or ethnicity. In total, 83% of PWH had a viral load <50 copies/mL, and 94% had a recent CD4 ≥200 cells/µL. The PWH group had a higher EAA, EEAA, GrimAge, and PhenoAge, and a lower DNAm-TL compared to the controls. IEAA was not different between groups. For PWH, there were significant negative correlations between IEAA and executive function, attention, and working memory and PhenoAge and attention. No associations between biomarkers and frailty were detected.
CONCLUSIONS
Evidence of epigenetic age acceleration was observed in AA older PWH using DNAm-based biomarkers of aging. There was no evidence of age acceleration independent of cell type National Institutes of Health composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function among PWH.
背景
已有人报告，在感染人类免疫缺陷病毒（HIV，HIV 感染者）的人群中，使用基于 DNA 甲基化（DNAm）的生物标志物可加速表观遗传衰老，但在非裔美国人（AA）、女性和年长的 HIV 感染者中，相关数据有限。
方法
在纽约市，对 107 名（69 名 HIV 感染者和 38 名 HIV 血清阴性对照者）年龄≥60 岁的 AA 成年人使用 Illumina EPIC 阵列进行 DNAm 测量。估计了 6 种基于 DNAm 的衰老生物标志物：（1）表观遗传年龄加速（EAA），（2）外在表观遗传年龄加速（EEAA），（3）内在表观遗传年龄加速（IEAA），（4）GrimAge，（5）PhenoAge，和（6）DNAm 估计端粒长度（DNAm-TL）。还进行了美国国立卫生研究院（NIH）认知工具箱（域：执行功能、注意力、工作记忆、处理速度和语言）和蒙特利尔认知评估（MoCA）的测试。采用 Fried 标准评估参与者的虚弱程度。
结果
HIV 感染者组和对照组在性别、实际年龄和种族方面没有差异。共有 83%的 HIV 感染者病毒载量<50 拷贝/mL，94%的 HIV 感染者最近 CD4 细胞计数≥200 个/µL。HIV 感染者组的 EAA、EEAA、GrimAge 和 PhenoAge 更高，而 DNAm-TL 更低。两组间的 IEAA 无差异。对于 HIV 感染者，IEAA 与执行功能、注意力和工作记忆以及 PhenoAge 与注意力呈显著负相关。未发现生物标志物与虚弱之间存在关联。
结论
在使用衰老的 DNAm 生物标志物时，AA 年长的 HIV 感染者存在表观遗传年龄加速的证据。没有证据表明与细胞类型组成无关的加速衰老（IEAA）与 HIV 相关，但该指标与 HIV 感染者认知功能下降有关。
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