骨骼肌中 NAD 水平降低和生理性脆弱增加与无症状中年成年人的病毒合并感染有关。

Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults.

机构信息

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

出版信息

J Acquir Immune Defic Syndr. 2022 Feb 1;89(Suppl 1):S15-S22. doi: 10.1097/QAI.0000000000002852.

DOI:10.1097/QAI.0000000000002852

PMID:35015741

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8751286/

Abstract

BACKGROUND

People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared with their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared with uninfected people remain understudied.

SETTING

The study site was Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

METHODS

We evaluated skeletal muscle tissue for levels of total nicotinamide adenine dinucleotide (NAD), NAD+, and nicotinamide adenine dinucleotide (NADH) in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus and/or cytomegalovirus and compared them with uninfected control participants.

RESULTS

Of the 54 persons with muscle biopsy data, the mean age was 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection and was exacerbated by hepatitis C virus and cytomegalovirus coinfection, with lowest levels of total NAD, NAD+, and NADH among persons who were coinfected with all 3 viruses (P = 0.015, P = 0.014, and P = 0.076, respectively). Levels of total NAD, NAD+, and NADH in skeletal muscle were inversely associated with inflammation (P = 0.014, P = 0.013, and P = 0.055, respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P < 0.001 and sCD163: P < 0.001) and immune activation (CD38 and human leukocyte antigen-DR expression on CD8 T cells: P < 0.001). In addition, coinfection was associated with increased physiologic frailty based on the Veteran Aging Cohort Study 1.0 index assessment (P = 0.001).

CONCLUSIONS

Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.

摘要

背景

与未感染的人相比，HIV 感染者（PLWH）患有多种疾病和生理功能下降的负担不成比例，但导致 PLWH 肌肉功能下降的生物学机制与未感染的人相比仍研究不足。

地点

本研究地点为马萨诸塞州波士顿哈佛医学院布莱根妇女医院。

方法

我们评估了中年无症状 PLWH 的骨骼肌组织中总烟酰胺腺嘌呤二核苷酸（NAD）、NAD+和烟酰胺腺嘌呤二核苷酸（NADH）的水平，并将其与未感染的对照组参与者进行比较。

结果

在有肌肉活检数据的 54 人中，平均年龄为 57 岁，女性占 33%。NAD 水平在 HIV 感染相关的骨骼肌中下降，并因丙型肝炎病毒和巨细胞病毒合并感染而加剧，在同时感染这 3 种病毒的人群中，NAD、NAD+和 NADH 的总水平最低（P = 0.015、P = 0.014 和 P = 0.076）。骨骼肌中总 NAD、NAD+和 NADH 的水平与炎症呈负相关（P = 0.014、P = 0.013 和 P = 0.055）。合并感染也与炎症标志物（CD4/CD8 比值：P < 0.001 和 sCD163：P < 0.001）和免疫激活标志物（CD38 和人类白细胞抗原-DR 在 CD8 T 细胞上的表达：P < 0.001）相关。此外，根据退伍军人老龄化队列研究 1.0 指数评估，合并感染与生理脆弱性增加有关（P = 0.001）。