Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1132-41. doi: 10.1073/pnas.1217154110. Epub 2013 Feb 25.
Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.
睡眠不足和昼夜节律紊乱与负面健康结果有关，包括肥胖、心血管疾病和认知障碍，但相关机制在很大程度上仍未得到探索。26 名参与者接受了 1 周的睡眠不足（睡眠限制条件下 5.70 小时，SEM = 每 24 小时 0.03 小时睡眠）和 1 周的充足睡眠（对照条件下 8.50 小时睡眠，SEM = 0.11）。在完全睡眠剥夺期间，在控制光、活动和食物影响的情况下，在每个条件之后，立即从每个参与者采集 10 个全血 RNA 样本。转录组分析显示，711 个基因受到睡眠不足的上调或下调。睡眠不足还使具有昼夜表达谱的基因数量从 1855 个减少到 1481 个，降低了这些基因的昼夜振幅，并使对随后的完全睡眠剥夺有反应的基因数量从 122 个增加到 856 个。受睡眠不足影响的基因与昼夜节律（PER1、PER2、PER3、CRY2、CLOCK、NR1D1、NR1D2、RORA、DEC1、CSNK1E）、睡眠稳态（IL6、STAT3、KCNV2、CAMK2D）、氧化应激（PRDX2、PRDX5）和代谢（SLC2A3、SLC2A5、GHRL、ABCA1）有关。受影响的生物过程包括染色质修饰、基因表达调控、大分子代谢以及炎症、免疫和应激反应。因此，睡眠不足会影响人体血液转录组，扰乱其昼夜节律调节，并加剧急性完全睡眠剥夺的影响。确定的生物学过程可能与睡眠不足对健康的负面影响有关，并强调睡眠稳态、昼夜节律和代谢之间的相互关系。
