Department of Medicine University of California San Diego, 9500 Gilman Drive La Jolla, CA, 92093, USA; San Diego Veterans Affairs Healthcare System, San Diego, CA, 92131, USA.
Department of Psychiatry University of California San Diego, 9500 Gilman Drive La Jolla, CA, 92093, USA.
Drug Alcohol Depend. 2021 Apr 1;221:108639. doi: 10.1016/j.drugalcdep.2021.108639. Epub 2021 Feb 16.
HIV infection and methamphetamine dependence (METH) are each associated with inflammation and premature aging, but their impact on biological aging is difficult to measure. Here we examined the impact of HIV and METH on leukocyte telomere lengths (LTL), and the correlations between LTL and other aging biomarkers.
The study was a cross-sectional analysis of 161 individuals categorized by HIV and methamphetamine (METH) dependence status into four groups: HIV-METH- (n = 50), HIV-METH+ (n = 29), HIV + METH- (n = 40), and HIV + METH+ (n = 42). We analyzed the relationships of leukocyte telomere length (telomere to single copy gene [T/S] ratio) with demographic and clinical data as well as a panel of biomarkers of inflammation and endothelial activation measured in blood and cerebrospinal fluid (CSF).
HIV and METH were independently associated with shorter T/S ratio, even after adjusting for demographics and leukocyte count (R = 0·59, p < 0·0001). Higher plasma C-reactive protein (p = 0·0036) and CSF VCAM-1 (p = 0·0080) were also associated with shorter T/S ratio. A shorter T/S ratio was associated with higher risk for cardiovascular disease (p < 0·0001) and stroke (p < 0·0001), worse motor functioning (p = 0·037) and processing speed (p = 0·023), more depressive symptoms (p = 0·013), and higher CSF neurofilament-light (p = 0·003).
HIV and METH dependence were each associated with shorter telomeres. After adjusting for demographics, HIV, and METH, T/S ratio remained associated with aging-related outcomes including neurocognitive impairment, neurodegeneration, risks of cardiovascular disease and stroke. While not establishing causality, this study supports using the T/S ratio as a biomarker for estimating the impact of HIV and comorbidities on long-term health.
HIV 感染和甲基苯丙胺(METH)依赖均与炎症和早衰有关,但它们对生物衰老的影响难以衡量。在此,我们研究了 HIV 和 METH 对白细胞端粒长度(LTL)的影响,以及 LTL 与其他衰老生物标志物的相关性。
本研究为横断面分析,共纳入 161 名个体,根据 HIV 和 METH 依赖状况分为四组:HIV-METH-(n=50)、HIV-METH+(n=29)、HIV+METH-(n=40)和 HIV+METH+(n=42)。我们分析了白细胞端粒长度(端粒与单拷贝基因[T/S]的比值)与人口统计学和临床数据以及血液和脑脊液(CSF)中炎症和血管内皮激活的一系列生物标志物之间的关系。
即使在调整了人口统计学和白细胞计数后,HIV 和 METH 仍与较短的 T/S 比值独立相关(R=0.59,p<0.0001)。较高的血浆 C 反应蛋白(p=0.0036)和 CSF VCAM-1(p=0.0080)也与较短的 T/S 比值相关。较短的 T/S 比值与更高的心血管疾病风险(p<0.0001)和中风风险(p<0.0001)、更差的运动功能(p=0.037)和处理速度(p=0.023)、更多的抑郁症状(p=0.013)和更高的 CSF 神经丝轻链(p=0.003)相关。
HIV 和 METH 依赖均与端粒较短有关。在调整人口统计学、HIV 和 METH 后,T/S 比值与神经认知障碍、神经退行性变、心血管疾病和中风风险等与衰老相关的结局仍相关。虽然不能确定因果关系,但本研究支持将 T/S 比值作为估计 HIV 和合并症对长期健康影响的生物标志物。