Tirzepatide to Slow Biological Aging

The Moody Longevity Trial: Tirzepatide to Slow Biological Aging

This pilot clinical study aims to investigate the potential effects of tirzepatide on biological aging in older adults. In this novel study, 90 adults aged 55-70 years with an indication for tirzepatide weight-loss therapy will be randomized to receive either tirzepatide 2.5 mg subcutaneously (SC) weekly or no drug for 24 weeks, followed by 12 weeks off the drug. Since tirzepatide is already recognized as a highly effective weight-loss agent in this population, the primary focus will not be on measuring weight loss. Instead, the study will document the effects of tirzepatide on markers of aging, physical function, and overall health.

Study Overview

• Status: Recruiting
• Conditions: Aging; LONGEVITY 1
• Intervention / Treatment: Drug: Zepbound

Detailed Description

Primary Objective To estimate the potential effect of tirzepatide on biological aging using epigenetic age (based on established DNA methylation-based clocks), among people 55-70 years of age with an indication for tirzepatide weight loss therapy.

The principal investigator (PI) will measure DNA methylation-based aging clocks (DNAmAge, DNAm PhenoAge, DNAm GrimAge and DunedinPACE) before and after a 24-W course of tirzepatide. The primary analysis will determine whether tirzepatide treatment leads to a statistically significant change in biological age as indicated by these clocks. The PI will specifically assess epigenetic age acceleration (epigenetic age minus chronological age) and the pace of aging metric.

Secondary and Exploratory Objectives

Among people 55-70 years of age with an indication for tirzepatide weight loss therapy, the is aim to:

1. Estimate self-reported tolerability and acceptability of tirzepatide during the study period
2. Estimate changes in BMI and weight over 24 W of tirzepatide therapy, and in off-drug follow-up, between W 24 and 36
3. Estimate changes in physical function over 24 W of tirzepatide and, in off-drug follow-up, between W 24 and 36
4. Estimate changes in inflammatory, aging and neurocognitive biomarker profiles over 24 W of tirzepatide therapy, and in off-drug follow-up, between W 24 and 36
5. Estimate changes in other biological hallmarks/markers of aging
6. Explore relationships between the above outcomes

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lamonne Crutcher; Phone Number: (409)772-1619; Email: lmcrutch@utmb.edu

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • Recruiting
      • University of Texas Medical Branch
      • Contact: Lamonne Crutcher; Phone Number: 409-772-1619; Email: lmcrutch@utmb.edu
      • Principal Investigator: Thomas Blackwell, MD, FACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 55-70 years
2. BMI ≥ 30 kg/m² or ≥ 27 kg/m² if also with ≥ 1 weight-related comorbidity
3. If taking anti-inflammatory or blood-pressure-/lipid-/glucose-lowering medications, no change in dose for ≥12 weeks prior to entry and no plans to dose escalate for the study duration
4. Willing and able to provide written informed consent and undergo all required study procedures

Exclusion Criteria:

1. BMI >35 kg/m²
2. Uncontrolled or end-stage, comorbid, cardiometabolic disease, in the opinion of the site investigator
3. Significant neurocognitive impairment, in the opinion of the site investigator
4. Current or planned use of medications for the treatment of obesity, or medications likely to cause significant changes in weight, during the study period (see prohibited medications, section 6.0)
5. Use of insulin
6. Plans to newly engage in formal, intensive physical activity or diet (such as ketogenic or very low carbohydrate) programs during the study period
7. Active eating disorder
8. Use of human growth hormone, tesamorelin, supraphysiologic testosterone or estradiol (stable doses for contraception, hypogonadism or other indications for exogenous sex steroid replacement therapy permitted) or anabolic steroids <12 W prior to entry, unless on a stable dose for >24 W prior to entry, or plans to start any of these medications while on study
9. Active, severe delayed gastric emptying
10. Prior bariatric surgery or major gastric surgery or plans for weight reduction surgery while on study
11. Known diabetic retinopathy
12. Personal or first-degree relative history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
13. Untreated, poorly controlled or previously undiagnosed thyroid disease
14. History of chronic pancreatitis
15. History of suicidal attempts or active suicidal ideation, in the opinion of the site investigator
16. Known allergy/sensitivity to GLP-1RA or GIPRA
17. Use or planned use of any immunomodulatory therapy or investigational therapy during the study period or use of an investigational therapy within 30 days of entry
18. Any other medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation.
19. Pregnancy, nursing or plans for either during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tirzepatide; Participants will receive Tirzepatide 2.5 mg weekly for 24 weeks, followed by a 12-week off-drug follow-up.	Drug: Zepbound; Auto injectors with a 2.5 mg dosage are given subcutaneously weekly.; Other Names: Tirzepatide
No Intervention: Placebo; Participants will be monitored for a total of 36 weeks without receiving medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in DNA Methylation-Based Biological Age	Change in biological age as measured by DNA methylation-based aging clocks (DNAmAge, DNAm PhenoAge, DNAm GrimAge, and DunedinPACE) following tirzepatide treatment.	Immediately before and after the study visit at Weeks 4, 12, and 24

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: Thomas Blackwell, MD, FACP, University of Texas Medical Branch, Galveston

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: October 15, 2025
• First Submitted That Met QC Criteria: October 21, 2025
• First Posted (Actual): October 24, 2025

Study Record Updates

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

More Information

Terms related to this study

• Keywords: DNA Methylation; GLP-1 Agonist; Biological Clock Deceleration
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: 25-0169

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes