Background

Stress is a key precipitant for many common diseases but established biological markers to track stress and guide investigations into mechanism linking stress and disease are lacking. Crosssectional studies have identified correlations between stress and telomere attrition, but no large, longitudinal studies examining the impacts of chronic stress on telomere length exist. Residency training for physicians is a well-established stressful experience and can be used as a prospective stress model.

应激是许多常见疾病的重要诱发因素,但目前还没有建立起跟踪应激和指导应激与疾病联系机制研究的生物学标记。横断面研究已经确定了压力和端粒磨损之间的关系,但没有大型的纵向研究考察慢性压力对端粒长度的影响。住院医师培训是一种公认的压力经历,可以作为一种预期的压力模型。

Medical residency, the first phase of professional medical training in the United States, is a stressful period in the career of physicians. Residents are faced with long work hours, sleep deprivation, and a new degree of responsibility for patients.

住院医师是美国职业医学培训的第一阶段,是医生职业生涯中充满压力的时期。住院医生面临着长时间的工作,睡眠不足,以及对病人的责任。(看过实习医生格蕾的小伙伴应该深有体会)

Telomeres are complexes consisting of tandem DNA nucleotide TTAGGG repeats complexed with proteins found at the ends of chromosomes that help ensure stability and maintenance of the nuclear genome. Telomere length decreases with each cell replication cycle, and once telomeres reach a critically shortened length, cells enter a state of replicative senescence。

端粒是由串联DNA核苷酸TTAGGG重复序列与在染色体末端发现的蛋白质结合的复合物,有助于确保和维持核基因组的稳定性。端粒长度随着细胞复制周期而缩短,一旦端粒长度缩短达到临界值,细胞就进入复制性衰老状态。

Methods

In a longitudinal cohort study of 250 interns (first-year residents) at 55 U.S hospital systems serving during the 2015-16 academic year, we examined associations between measures of the residency experience and saliva-measured telomere attrition.

对美国55所大学的250名实习生(第一年住院医生)进行的一项纵向队列研究中。在2015-16学年,我们调查了住院医生的实习经历和唾液所含细胞的端粒磨损之间的关系。

Baseline Assessment

All surveys were conducted through a secure, web-based platform designed to maintain confidentiality. Subjects completed a baseline survey upon study enrollment prior to commencing internship.The survey assessed general demographic factors (age, sex, and marital status), specialty, self-reported history of depression, and various psychological measures.

所有调查都是通过一个安全的、基于web的保密性平台进行的。受试者在开始实习前完成了基线调查。调查评估了一般的人口学因素(包括年龄、性别、婚姻状况)、专业、自我报告的抑郁史和各种心理测试。

Within- Internship Assessments

Participants were contacted via e-mail at months 3, 6, 9, and 12 of their internship year and asked to complete a web-based survey that included the PHQ-9, week average work hours and sleep, and outside residency stressful life events (defined as a serious illness, death or serious illness in a close family member or friend, financial problems, end of a serious relationship, or becoming a victim of crime or domestic violence) during the past 3 months。

在实习的第3, 6, 9和第12个月,参与者被要求完成一个通过电子邮箱发送的调查,其中包括PHQ-9,每周平均工作时间和睡眠时间,和在过去的3个月内发生的其他的压力生活事件(定义为严重的疾病,死亡或亲密家庭成员或朋友的严重疾病,经济问题,失恋,或成为犯罪或家庭暴力的受害者)。

DNA Collection and Telomere Length Analysis

Subjects submitted Oragene OG-500 salivary DNA self-collection kit saliva samples via postal mail for telomere assessment 2-6 weeks before internship and at the completion of Internship.

受试者于实习前2-6周及实习结束时,以邮寄的方式寄送Oragene OG-500唾液DNA自收集试剂盒唾液样本进行端粒检测。

Results

Telomere length shortened significantly over the course of internship year, from 6465.1 ± 876.8 base pairs before internship to 6321.5 ± 630.6 base pairs at the end of internship (t(246) = 2.69; P=0.008). Stressful early family environments and neuroticism were significantly associated with

shorter pre-internship telomere length. Longer work hours were associated with greater telomere intern telomere loss over the year (p = 0.002). Of note, the mean telomere attrition during internship year was six times greater than the typical annual attrition rate identified in a recent meta-analysis.

端粒长度在实习期间明显缩短,从实习前的6465.1±876.8个碱基对到实习结束时的6321.5±630.6个碱基对(t(246) = 2.69; P=0.008). 早期紧张的家庭环境和神经质与实习前较短的端粒长度显著相关。工作时间越长,端粒耗损越大。(p = 0.002). 值得注意的是,实习期间的端粒平均耗损是最近一项荟萃分析中表明特有每年耗损的六倍。

Conclusions

This work implicates telomere attrition as a biologically measurable consequence of physician training, with the magnitude of attrition associated with workload. Identification of an objective, biological sequelae of residency stress may help to facilitate the development of effective interventions. Further, the findings implicate telomere attrition as an objective biomarker to follow the pathologic effects of stress, in general.

这项研究表明端粒磨损可以作为医师培训的一种生物学测量结果。并将其与工作量相关的磨损程度联系起来。住院医师压力的客观确定、住院医师压力的生物学后遗症可能有助于促进有效干预措施的发展。此外,研究结果表明,端粒磨损是一种客观的生物标志物,可以跟踪应激的病理效应。