Restoring Molecular Circadian Rhythm

Study Overview
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Brief Summary
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The goal is to address the mechanisms that account for alteration of circadian rhythms with age. As the blood of aged individuals can produce this alteration, the investigators propose to use such blood samples to age circadian rhythms in cultured cells. The investigators will verify aged blood-dependent alteration of rhythms and then conduct molecular screens to reverse this decline. If the investigators identify specific genes that can restore molecular circadian rhythm in vitro, the investigators will explore these in animal models (Drosophila, mouse).

Official Title
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Exploratory Pilot Study to Discover Genes That Restore the Molecular Circadian Rhythm

Conditions
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Healthy Young, Healthy Elderly

Intervention / Treatment
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* Other: Observational study without intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General good health with the following conditions permissible cardiovascular risk prevention, intake of low dose aspirin, hypertension, intake of beta-blockers, ACE inhibitors, diuretics, calcium channel blockers hypercholesterinemia, intake of statins Cases: 70-85 years of age Controls: 20-35 years of age Patients must be able to read and understand English Participants must sign the informed consent form Participants must have a wrist-actigraphy-based average TST (total sleep time) ≥ 6 hours per night (measured over 7 consecutive days) occurring between 22:00 - 08:00 Exclusion Criteria: Known history of severe psychiatric or cognitive conditions, for example mania, schizophrenia, or mental retardation Shift work, defined as recurring work between 22:00-05:00 History of clinically significant obstructive sleep apnea Transmeridian travel across ≥2 time zones in the two weeks prior to the blood draws and one week after, > 2 drinks of alcohol per day Use of illicit drugs

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Young<br>Observational study without intervention | Other: Observational study without intervention<br>* Observational study without intervention<br>|
| Elderly<br>Observational study without intervention | Other: Observational study without intervention<br>* Observational study without intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta of period length measured in hh:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults) | To determine if serum collected from young versus old healthy study participants have a differential effect on the expression of circadian rhythms in an in vitro culture of a fibroblast cell line | Time point 14:00 Hours | 
| Delta of phase measured in HH:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults) | The primary endpoint will be the difference in phase angle in vitro between cycling fibroblasts and incubated with serum collected from cases (old adults) versus controls (young adults) | Time point 14:00 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronotype | Assessed per survey; chronotypes per Munich Chronotype questionnaire are extreme early type, moderate early type, slight early type, normal type, slight late type, moderate late type, extreme late type | 4 weeks | 
| Acrophase | Clock hour of peak physical activity averaged from 7 or more days of actigraphy | 7 days | 
| Physical activity | Vector magnitude of physical activity averaged from 7 or more days of actigraphy | 7 days | 
| Sleep quantity | Hours of sleep averaged from 7 or more days of actigraphy | 7 or more days | 
| Sleep quality: actigraphy | Sleep fragmentation averaged from 7 or more days of actigraphy | 7 days | 
| Ambient light exposure | Ambient light exposure averaged from 7 or more days of actigraphy | 7 days | 
| Heart rate variability | Heart rate variability (RR intervals) averaged from 24 hours of BioPatch | 24 hours | 
| Saliva cortisol | Difference in concentrations of cortisol measured in saliva between morning versus evening | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy, young, elderly