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.
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.
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。
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.
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.
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.
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。
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.