Restoring Molecular Circadian Rhythm

Overview

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, we propose to use such blood samples to "age" circadian rhythms in cultured cells. We will verify aged blood-dependent alteration of rhythms and then conduct molecular screens to reverse this decline. If we identify specific genes that can restore molecular circadian rhythm in vitro, we will explore these in animal models (Drosophila, mouse).

Full Title of Study: “Exploratory Pilot Study to Discover Genes That Restore the Molecular Circadian Rhythm”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: August 17, 2021

Interventions

  • Other: Observational study without intervention
    • Observational study without intervention

Arms, Groups and Cohorts

  • Young
    • Observational study without intervention
  • Elderly
    • Observational study without intervention

Clinical Trial Outcome Measures

Primary Measures

  • 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 Frame: 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
  • 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 Frame: 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)

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Pennsylvania
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Carsten Skarke, MD, Principal Investigator, University of Pennsylvania
  • Overall Contact(s)
    • LaVenia Banas, 215-662-4652, banas@pennmedicine.upenn.edu

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