Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels. Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms. Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders. Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being. In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach. Evidence from preclinical and translational science is applied to a clinical and population-based approach. Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes.

Acoustic stimulation methods applied during sleep in young adults can increase slow wave activity (SWA) and improve sleep-dependent memory retention. It is unknown whether this approach enhances SWA and memory in older adults, who have a reduction in SWA. Additionally, older adults are at risk for age-related cognitive impairment and therefore may benefit from non-invasive interventions. The aim of this study was to use acoustic stimulation to increase SWA and improve declarative memory in healthy older adults. Thirteen participants 60-84 years old completed one night of acoustic stimulation and one night of sham stimulation in random order. During sleep, a real-time algorithm using an adaptive phase-locked loop modeled the phase of endogenous slow waves in midline frontopolar electroencephalographic recordings. Pulses of pink noise were delivered when the upstate of the slow wave was predicted. Each interval of 5 pulses (“ON interval”) was followed by a pause of approximately equal length (“OFF interval”). SWA during the entire sleep period was similar between stimulation and sham conditions, whereas SWA and spindle activity were increased during ON intervals compared to matched periods during the sham night. The increases in SWA and spindle activity were sustained across almost the entire five pulse ON interval compared to matched sham periods. Verbal paired-associate memory was tested before and after sleep. Overnight improvement in word recall was significantly greater with acoustic stimulation compared to sham and was correlated with corresponding change in SWA between ON and OFF intervals. Using the phase-locked-loop method to precisely target acoustic stimulation to the upstate of sleep slow oscillations, we were able to enhance SWA and improve sleep-dependent memory storage in older adults, which strengthens the theoretical link between sleep and age-related memory integrity.

Significance: Ambient nighttime light exposure is implicated as a risk factor for adverse health outcomes, including cardiometabolic disease. However, the effects of nighttime light exposure during sleep on cardiometabolic outcomes and the related mechanisms are unclear. This laboratory study shows that, in healthy adults, one night of moderate (100 lx) light exposure during sleep increases nighttime heart rate, decreases heart rate variability (higher sympathovagal balance), and increases next-morning insulin resistance when compared to sleep in a dimly lit (<3 lx) environment. Moreover, a positive relationship between higher sympathovagal balance and insulin levels suggests that sympathetic activation may play a role in the observed light-induced changes in insulin sensitivity.