The Physiological Chronobiome Modified by Age, Sex and Under Evoked Conditions

The investigators piloted the characterization of the human chronobiome. Now, this line of research is extended to explore physiological chronobiome modulated by sex, age and under evoked conditions.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy; Healthy Aging
• Intervention / Treatment: Other: Fatty meal to challenge the physiological chronobiome in healthy young and old

Detailed Description

"Is your body clock important? Absolutely. Just ask any morning lark who lives with a night owl, or vice versa". This quote from a piece published in the Philadelphia Inquirer about the investigator's work illustrates the importance of time in one's personal preferences [https://www.inquirer.com/health/chronobiome-body-clock-university-pennsylvania-20190307.html].

Several decades of research have found out that how well a person functions, very much depends on how much this person is in harmony with her/his own preferences and environment. This harmony is acutely disturbed when one travels quickly across several time zones, because suddenly the body's physiology is still following the departure time but the arrival time tells the body something different. As a result, travelers often experience sleep problems and indigestion, which usually disappear after a couple of days. This is different in long-term shift workers for whom work outside of the typical daylight hours means that they have a higher risk for diseases including cardiovascular diseases, diabetes and cancer.

Another observation has been that many diseases occur or worsen at a specific time of day. Heart attacks, for example, most often occur when patients wake up in the morning. Shortness of breath peaks at 4 am in the morning for patients with asthma.

Intriguingly, more and more studies suggest that time of day matters how effective drugs work and how many side effects one might experience. To study this the investigators started to describe the human chronobiome, which foremost looks at time of day differences of a person's physiology, for example, in the small pilot study the investigators saw a difference in break down products, or metabolites, between mornings and evenings. Now, in this present study, the investigators wish to extend the understanding how the human chronobiome differs between healthy men and women, healthy young and old and how it reacts to a fatty meal challenge.

This knowledge will help the investigators to say when a finding can still be considered normal or maybe indicates a first sign of disease. The novelty of this approach is that the investigators measure long enough to understand the role of time of day for a person's chronobiome, that the investigators measure many things to obtain a comprehensive representation of a person's chronobiome, that every measure is timestamped, and that the investigators ask participants to eat fatty meals to see how the chronobiome changes.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Young: 18-30 years of age, Old: 55-75 years of age
2. Apparent healthy
3. BMI (body mass index) up to 27.4
4. Upper arm with intact skin, i.e. without areas of breached or injured skin visible, for ambulatory blood pressure (ABP) measurements,
5. Own and use a smartphone.

Exclusion Criteria:

1. History of severe psychiatric illness or cognitive conditions, for example (mania, schizophrenia, or mental retardation;
2. Shift work, defined as recurring work between 22:00-05:00;
3. A diagnosis of clinically significant obstructive sleep apnea;
4. Serum creatinine > 1.5 mg/dl in men or >1.3 mg/del in women;
5. Significant liver disease (>3x upper limit of normal);
6. Diabetes mellitus;
7. Past diagnosis of gastroesophageal reflux disease,
8. Transmeridian travel across ≥3 time zones in the two weeks before the 48hr deep phenotype sessions;
9. Use of oral or intravenous antibiotics in the 6 months prior to enrollment;
10. Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening;
11. > 2 drinks of alcohol per day;
12. Use of drugs assessed in the urinary drug test;
13. Nursing or pregnant (pregnancy will be repeatedly assessed at the beginning of each of the four inpatient visits, i.e. prior to the start of blood draws);
14. Use of pacemaker or implantable Cardioverter Defibrillator (ICD);
15. Bilateral mastectomy;
16. History of Raynaud's phenomenon;
17. Known allergy against natural latex rubber (contained in ABP bladder and tubing);
18. Subjects taking medication with alpha-blockers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fatty meal; To study how a fatty meal modifies the physiological chronobiome in young and old, an isocaloric controlled liquid high fat meal (ICLHFM) will be consumed within 5 min. The ICLHFM contains an equivalent to 35% of the estimated total daily energy requirements (TDE), 60% of kcal delivered from fat while 13% come from protein and 27 % from carbohydrate.	Other: Fatty meal to challenge the physiological chronobiome in healthy young and old; The intervention consists of a fatty meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent difference in the number of proteins with post-translational modifications found in blood samples from young versus old participants	High-throughput proteomics analysis determines the number of proteins with and without post-translational modifications. This will explore what effect age has on the number of proteins with post-translational modifications.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent difference in the number of proteins with post-translational modifications found in blood samples from female versus male participants	High-throughput proteomics analysis determines the number of proteins with and without post-translational modifications. This will explore what effect sex has on the number of proteins with post-translational modifications.	48 hours
Percent difference in the number of proteins with post-translational modifications found in blood samples from female versus male participants and by age	High-throughput proteomics analysis determines the number of proteins with and without post-translational modifications. This will explore whether an interaction between age and sex has an effect on the number of proteins with post-translational modifications.	48 hours
Percent difference in environmental light exposure between young versus old participants	Wrist actigraphy collects personal light exposure	48 hours
Percent difference in environmental light exposure between young versus old participants and by sex	Wrist actigraphy collects personal light exposure	48 hours
Percent difference in physical activity between young versus old participants	Wrist actigraphy records accelerometer data to calculate physical activity	48 hours
Percent difference in physical activity between young versus old participants and by sex	Wrist actigraphy records accelerometer data to calculate physical activity	48 hours
Percent difference in systolic blood pressure readings between young versus old participants	Ambulatory blood pressure measurements (ABPM) collect blood pressure readings	48 hours
Percent difference in systolic blood pressure readings between young versus old participants and by sex	Ambulatory blood pressure measurements (ABPM) collect blood pressure readings	48 hours

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Garret A FitzGerald, MD, University of Pennsylvania; Principal Investigator: Carsten C Skarke, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Skarke C, Lahens NF, Rhoades SD, Campbell A, Bittinger K, Bailey A, Hoffmann C, Olson RS, Chen L, Yang G, Price TS, Moore JH, Bushman FD, Greene CS, Grant GR, Weljie AM, FitzGerald GA. A Pilot Characterization of the Human Chronobiome. Sci Rep. 2017 Dec 7;7(1):17141. doi: 10.1038/s41598-017-17362-6.

Helpful Links

• Philadelphia Inquirer

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2020
• Primary Completion (Estimated): January 4, 2027
• Study Completion (Estimated): June 4, 2028

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Multiomics; Chronobiome; Molecular networks; Circadian clocks; Remote sensing
• Other Study ID Numbers: 834156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No