Restoring Molecular Circadian Rhythm

Suspended

Brief Summary: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Young	Observational study without intervention	Observational study without intervention
Elderly	Observational study without intervention	Observational study without intervention

Primary Outcome Measures

Name	Time	Method
Delta of phase measured in HH:mm between in vitro cycling fibroblasts incubated with serum collected from cases (elderly adults) versus controls (young adults)	Time point 14:00 Hours	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)
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)	Time point 14:00 Hours	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

Secondary Outcome Measures

Name	Time	Method
Physical activity	7 days	Vector magnitude of physical activity averaged from 7 or more days of actigraphy
Sleep quantity	7 or more days	Hours of sleep averaged from 7 or more days of actigraphy
Chronotype	4 weeks	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
Acrophase	7 days	Clock hour of peak physical activity averaged from 7 or more days of actigraphy
Sleep quality: actigraphy	7 days	Sleep fragmentation averaged from 7 or more days of actigraphy
Heart rate variability	24 hours	Heart rate variability (RR intervals) averaged from 24 hours of BioPatch
Ambient light exposure	7 days	Ambient light exposure averaged from 7 or more days of actigraphy
Saliva cortisol	24 hours	Difference in concentrations of cortisol measured in saliva between morning versus evening

Locations (1): University of Pennsylvania School of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States

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