Aging, Circadian Disruption, Sleep Restriction
Conditions
Keywords
Sleep, Aging, Metabolism, Circadian, Genetic, Alertness
Brief summary
The overall objectives of the proposed study are to examine the consequences of chronic circadian disruption and chronic sleep restriction on metabolic function in healthy adults.
Detailed description
It has long been recognized that sleep patterns change with age. A common feature of aging is the advance of the timing of sleep to earlier hours, often earlier than desired. These age-related changes are found in even healthy individuals who are not taking medications and who are free from sleep disorders. In addition to these sleep disturbances, many older individuals curtail their sleep voluntarily, reporting similar rates of sleep restriction (sleeping less than 7 or less than 6 hours per night) when compared to young adults. Whether voluntary or not, insufficient sleep has medical, safety and metabolic consequences. In fact, converging evidence in young adults suggests that sleep restriction per se may impair metabolism, and that reduced sleep duration is associated with weight gain, obesity, diabetes, cardiovascular disease, and mortality. An understanding of how the circadian and sleep homeostatic neurobiological processes responds to increasing homeostatic sleep pressure, and the effects of sleep restriction on metabolism at different ages, should provide information on the regulation of sleep and metabolism in aging, as well as direction for future treatments. In the present study, we will study the separate impacts of chronic sleep restriction (while minimizing circadian disruption) and chronic circadian disruption (while minimizing sleep disruption) and a poor diet on metabolism.
Interventions
BEHAVIORALCircadian Disruption
Following a baseline of adequate time in bed, study participants will spend 3 weeks on a daily jet-lag schedule (where each day is longer than 24 hours).
BEHAVIORALSleep Restriction
Following a baseline of adequate time in bed, study participants will have a shortened opportunity for sleep during each 24-hour day (for three weeks).
BEHAVIORALControl
Following a baseline of adequate time in bed, study participants will continue to have adequate time in bed and opportunity for sleep during each 24-hour day, for 3 weeks.
Sponsors
National Institute on Aging (NIA)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults with conventional and regular sleep-wake timing * Non-smokers * Completion of medical, psychological, and sleep screening tests * Able to spend 37 consecutive days/nights in the laboratory
Exclusion criteria
* History of neurological or psychiatric disorder * History of sleep disorder or regular use of sleep-promoting medication * Current prescription, herbal, or over-the-counter medication use * Traveling across 2 or more time zones within past 3 months * Donating blood within past 8 weeks * Worked night or rotating shift work within past 3 years * Hearing impairment * Drug or alcohol dependency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin sensitivity | Baseline day 3, at 1 week and at 3 weeks of exposure, and 1 week into recovery | Euglycemic hyperinsulinemic clamp-assessed measure of insulin sensitivity |
| Changes in glucose levels after standardized meal | Baseline day 2, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | Frequent blood samples during and after standardized meal (breakfast), response of blood glucose levels |
| Change in insulin levels after standardized meal | Baseline day 2, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | Frequent blood samples during and after standardized meal (breakfast) |
| Change in 24h profiles of leptin | Baseline day 2, during acute circadian misalignment (exposure day 3), and acute realignment (exposure day 7) | Hourly blood samples for 24 hours |
| Change in 24h profiles of cortisol | Baseline day 2, at 3 weeks of exposure, and 1 week into recovery | Hourly blood samples for 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in inflammatory markers and wake-time hormone levels | Baseline days 2 and 3, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | Measurements on fasted blood samples |
| Changes in daily patterns of gene expression, epigenetic or proteomic markers | Baseline day 2, at 1 week and at 3 weeks of exposure, and 1 week into recovery | Blood samples collected every 4 hours for 48 hours |
| Change in resting metabolic rate | Baseline days 2 and 3, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | Indirect calorimetry, daily body weight, core body temperature |
| Change in nutrient absorption | Daily throughout the 3-day baseline, last 3 days of the 3-week exposure, and last three days of the 1-week recovery | Bomb calorimetry on stool samples |
| Changes in measures of sympathovagal balance and autonomic function | Baseline day 3, at 1 week and at 3 weeks of exposure, and 1 week into recovery | EKG, urinary catecholamines, fasting and postprandial blood samples for cortisol, epinephrine and norepinephrine |
| Change in circadian phase and/or period | Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery | Via measurement of core body temperature and melatonin (salivary and plasma) |
| Changes in sleep/wake architecture and brain electrical activity | Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery | Polysomnography during sleep and wake |
| Change in neurocognitive performance | Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery | Cognitive test battery presented via computer interface |
| Changes in perception of pain, hunger and sleepiness | Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery | Daily questionnaires |
Countries
United States
Outcome results
None listed