IMAT Quality in Aging

Targeting Intramuscular Adipose Quality in Aging

This study will test the central hypothesis that fat within the muscle, or intramuscular adipose tissue (IMAT), exhibits elevated damage and pro-inflammatory signaling with aging, both of which are reduced by progressive resistance exercise (PRE). Sixteen older adults 65-80 years old will be recruited and complete a 12 week calf PRE intervention. Calf muscle strength, composition (measured by computed tomography) and muscle biopsies will be collected before and after the intervention. Histology, transcriptomic and secretomic tests will be completed to assess signs of damage and inflammation.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging
• Intervention / Treatment: Other: Calf muscle strengthening

Detailed Description

Sixteen older adult (65-80 years) will be recruited from existing databases and screened for potential participation by phone. The Rapid Assessment of Physical Activity (RAPA) will be completed, to include those who are underactive (scores 3-5). Individuals who meet the inclusion criteria will attend an in-person screening where their calf muscle strength, physical performance and safety for muscle biopsy (via complete blood count with differential and prothrombin time/international normalized raio on blood draw) will be assessed. Individuals deemed safe to participate and who give informed consent will attend a second visit which will include a computed tomography (CT) scan of the lower leg and ultrasound-guided gastrocnemius muscle+IMAT biopsy. One week later, participants will begin the ankle plantarflexor-targeted progressive resistance exercise (PRE) program which will be delivered in a group Zoom format with a trained therapist 3 times per week for 12 weeks. One week following completion of the PRE program, participants will return for follow-up strength measures, CT, and biopsy. This will complete their participation. In the lab, biopsies will be subdivided for bulk ribonucleic acid sequencing (RNAseq), explant culture and histology. Bulk RNAseq will be used to identify age- and exercise-responsive genes that encode secreted proteins. These putative secreted signals will be validated by protein quantification in explant culture. The cellular origin of validated signals will then be mapped by RNA in situ hybridization (RNAscope) on the portion of the biopsy allocated to histology. Sections will also used to identify senescent cells, inflammatory macrophages and beige adipocytes.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mary Hastings, PT, DPT, MSCI, ATC; Phone Number: 1 314-286-1433; Email: hastingsmk@wustl.edu
• Study Contact Backup: Name: Gretchen Meyer, PhD; Phone Number: 1-314-286-1456; Email: meyerg@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Washington University
      • Contact: Mary Hastings, PT, DPT, MSCI, ATC; Phone Number: 314-286-1433; Email: hastingsmk@wustl.edu
      • Contact: Email: hastingsmk@wustl.edu
      • Sub-Investigator: Mary Hastings, PT, DPT, MSCI, ATC
      • Principal Investigator: Gretchen Meyer, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Rapid Assessment of Physical Activity scores between 3 and 5
• Able to don and doff the weighted vest
• Access to a smart phone and ability to navigate the phone to enter and manage a zoom intervention
• Commitment and availability to attend a virtual 40-minute intervention 3x per week for 12 weeks

Exclusion Criteria:

• Contraindications to radiation exposure (e.g. Women who are pregnant, previous high radiation exposure)
• Bleeding disorders
• Lower extremity trauma/surgery/injury or neuropathy that would impact muscle structure and function or ability to complete exercise intervention
• Diabetes mellitus, cardiovascular disease, peripheral vascular disease, cancer, stage 4 hypertension, anemia, connective tissue disorder
• Neurological disorder (e.g. stroke, Parkinson's disease, multiple sclerosis, spinal cord injury)
• Medications: insulin, glucagon-like peptide-1 (GLP1) agonists, sex hormone replacement therapy, chronic NSAIDs, anticoagulation therapy, cholesterol lowering medications such as statins
• Unable to safely perform the progressive resistance exercise (e.g. Vestibular or balance issues that make performing the intervention unsafe, severe osteoporosis or general fragility that limits weighted vest tolerance)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Calf muscle strengthening; Older adults will complete a 3x/wk, 12 week calf strengthening exercise over zoom. The intervention will be delivered in small groups. Older adult baseline data will be compared to post-intervention data to understand the impact of exercise on aging muscle and fat within the muscle	Other: Calf muscle strengthening; The calf intervention will be delivered 3x/wk for 12 weeks over zoom, in small groups. There are 3 exercises 1) standing heel rise, 2) seated heel rise, and 3) long sitting ankle plantarflexion. The exercises will be overloaded using a weighted vest, body weight, and/or theraband. Exercises will be progressed as strength improves.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biopsy: Senescent cell density	Senescent cells will be identified by expression of β-galactosidase (b-gal) and p16 on histological sections from muscle biopsies. B-gal and p16 positive cells will be counted and normalized to the histological region of interest to obtain a measure of density (# senescent cells / mm^2).	Baseline and post-intervention (approximately 14 weeks after baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total plantarflexor muscle volume (CT) (Cm^3)	Muscle volume of the calf and foot will be measured with computed tomography (CT). The participant is supine with leg extended into the (CT). Image post-processing includes removing bones and subcutaneous fat and then segmenting and measuring plantarflexor compartment muscle volume (cm^3).	Baseline and post-intervention (approximately 14 weeks after baseline)
Plantarflexor Compartment Intramuscular Fat Volume (cm^3)	Intramuscular fat volume of the calf will be measured with computed tomography (CT). The participant is supine with leg extended into the (CT). Image post-processing includes removing bones and subcutaneous fat and then segmenting and measuring plantarflexor compartment fat volume (cm^3).	Baseline and post-intervention (approximately 14 weeks after baseline)
Plantarflexor peak torque (Newton-meters)	Plantarflexor peak torque of the ankle will be assessed using isokinetic dynamometry. The participant will have a minimum of 3 practice trials to become familiar with the test. The participant will be given 3 minutes of rest and then 3 maximum plantarflexion contractions will be completed, the highest torque produced will be recorded (Newton-meters, Nm).	Baseline and post-intervention (approximately 14 weeks after baseline)
Stair Climb Power (W)	Stair climb power will be calculated by multiplying the participant's weight (N)X height of stairs (1.853 meters)/time is takes for them to climb the 10 steps.	Baseline and post-intervention (approximately 14 weeks after baseline)
Walking Speed (meters/second)	50 foot walking speed (meters/sec) will be measured. Route is 25 feet to a line, turn around, and return to start.	Baseline and post-intervention (approximately 14 weeks after baseline)
Physical Performance Test Total Score	Physical performance test total score is a composite from the following tests: bilateral feet together stance time, bilateral semi-tandem stance time, and bilateral tandem stance time, five time chair rise time, lift a book to a shelf time, don and doff a jacket time, 360 turn right and left examining stability and continuity, time to pick a nickle off the floor, 50 feet walking speed, stair climb speed. Score ranges from 32 (no fraility) to 0 (severe frailty)	Baseline and post-intervention (approximately 14 weeks after baseline)
Biopsy: Adipocyte size	Adipocyte boundaries will be identified by expression of perilipin on histological sections from muscle biopsies. Adipocyte area will be defined as the area inside a perilipin bounded shape and will be quantified for each adipocyte in the histological region of interest (mm^2).	Baseline and post-intervention (approximately 14 weeks after baseline)
Biopsy: Macrophage density	Macrophages will be identified by expression of CD206 and CD68 on histological sections from muscle biopsies. CD206 and CD68 positive cells will be counted and normalized to the histological region of interest to obtain a measure of density (# senescent cells / mm^2).	Baseline and post-intervention (approximately 14 weeks after baseline)
Biopsy: Beige adipocyte density	Beige adipocytes will be identified by expression of UCP1 on histological sections from muscle biopsies. UCP1 positive cells will be counted and normalized to the histological region of interest to obtain a measure of density (# senescent cells / mm^2).	Baseline and post-intervention (approximately 14 weeks after baseline)
Biopsy: Differentially expressed genes and pathways	Differentially expressed genes and pathways will be extracted from RNA sequencing performed on biopsy material (gene count).	Baseline and post-intervention (approximately 14 weeks after baseline)
Biopsy: cytokine secretion	Cytokines will be analyzed in the secreted medium from biopsy material using an antibody based detection method (pg/mL).	Baseline and post-intervention (approximately 14 weeks after baseline)
Biopsy: Spatially resolved gene expression	Spatially resolved gene expression will be measured on histological sections using an RNAscope (dots/cell).	Baseline and post-intervention (approximately 14 weeks after baseline)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Gretchen Meyer, PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: muscle; aging
• Other Study ID Numbers: 202512046; 1R21AG091159-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The following for participants at baseline

1. Demographics (Self-report responses to questionnaires for sex, age, race/ethnicity, socioeconomic status, medical history)

   The following for participants at baseline and post-treatment

2. Clinical measures (Data collected during laboratory examination. De-identified, aggregate summary data per time point will be shared in csv file format)
3. Strength measures (Ankle plantarflexor peak torque measurements. De-identified, aggregate summary data per time point will be shared in csv file format.)
4. Computed tomography measures (Measurements of muscle and adipose volumes. De-identified, aggregate summary data will be shared in csv file format.)
5. RNA sequencing, luminex secretome, histological imagines and RNA scope image

• IPD Sharing Time Frame: Data will be shared as soon as possible and no later than the time of publication or at the end of the funding period, whichever comes first
• IPD Sharing Access Criteria: All shared data will be de-identified and accessible in a controlled manner according to the guidance of Washington University's Human Research Protection Office (HRPO).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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