Data Sheet 2_Cellular senescence in acute human infectious disease: a systematic review.pdf

IntroductionAcute infectious disease represents a significant cause of mortality and morbidity in elderly individuals admitted to the hospital. In its extreme, it presents as sepsis, a systematic inflammatory and immunologic response responsible for self-injurious organ injury. As individuals age, a unique set of factors including immunosenescence predispose them to acquiring an infection and a worse clinical prognosis. This systematic review explores the relationship between cellular senescence, an age-related inflammatory phenomenon, with acute human infectious disease.
MethodsEmbase via OVID, Scopus, Web of Science, Global Index Medicus, Cochrane Library via Wiley, and ClinicalTrials.gov were queried. Included studies must have compared at least one of the following measures of cellular senescence between patients with an infection and without an infection: cell cycle inhibition measured via levels of p16INK4a and/or p21CIP1, short telomere length, DNA damage via ɣH2AX, high senescence-associated β galactosidase activity, and inflammation via the detection of senescence associated secretory phenotype (SASP). Manuscripts were screened and data collected via two independent reviewers.
ResultsA total of 15,828 studies were screened after duplicates were removed. One hundred and fifty-three full-text articles were assessed for eligibility and a total of 16 original articles were included in analysis. Of the 16 original articles included, 12 (75%) articles were centered on SARS-CoV-2, 2 (12.5%) articles utilized patients infected with Leishmania braziliensis, 1 (6.25%) with Plasmodium falciparum, and 1 (6.25%) with Hepatitis C.
ConclusionCurrent literature demonstrates robust upregulation of markers of cellular senescence in the setting of acute SARS-CoV-2, P. falciparum, L. braziliensis, and hepatitis C virus, and that markers of senescence correlate with disease severity and persist for months after resolution. Limitations in the number and types of infectious organisms studied, low sample sizes, modest longitudinal sampling, and a lack of consistency in markers measured, the method of measurement, and the definition of normal values represent ongoing gaps in the literature.
Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421473, Identifier CRD42023421473.

引言
急性传染病是导致住院老年患者死亡与发病的重要原因。其极端表现为脓毒症（sepsis）——一种可引发自身损伤性器官损伤的全身性炎症与免疫应答状态。随着年龄增长，免疫衰老（immunosenescence）等一系列独特因素会使老年人更易发生感染，且临床预后更差。本系统综述（systematic review）探讨了细胞衰老（cellular senescence）——一种与年龄相关的炎症现象——与人类急性传染病之间的关联。
方法
通过OVID平台的Embase数据库、Scopus数据库、Web of Science数据库、全球医学索引（Global Index Medicus）、Wiley旗下的Cochrane图书馆以及ClinicalTrials.gov平台进行文献检索。纳入研究需至少比较感染患者与非感染患者之间的一项细胞衰老标志物：通过p16INK4a和/或p21CIP1水平检测的细胞周期抑制状态、端粒长度缩短、通过ɣH2AX检测的DNA损伤、高衰老相关β-半乳糖苷酶活性，以及通过衰老相关分泌表型（SASP）检测的炎症水平。由两名独立评审员进行文献筛选与数据提取。
结果
去除重复文献后共筛选15828项研究，评估其中153篇全文文献的合格性，最终纳入16篇原创研究进行分析。在纳入的16篇原创研究中，12篇（75%）聚焦严重急性呼吸综合征冠状病毒2（SARS-CoV-2），2篇（12.5%）纳入巴西利什曼原虫（Leishmania braziliensis）感染患者，1篇（6.25%）纳入恶性疟原虫（Plasmodium falciparum）感染患者，1篇（6.25%）纳入丙型肝炎感染患者。
结论
现有文献表明，在急性严重急性呼吸综合征冠状病毒2、恶性疟原虫、巴西利什曼原虫及丙型肝炎病毒感染情境下，细胞衰老标志物显著上调；且衰老标志物与疾病严重程度相关，并在感染缓解后可持续数月。本研究存在以下局限性：所研究病原体的数量与类型有限、样本量偏小、纵向采样不足，以及检测标志物、检测方法及正常参考值定义缺乏一致性，这些仍是当前文献中存在的研究空白。
系统综述注册信息
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421473，标识符为CRD42023421473。