NCT07506681

IMAT Quality in Aging

Targeting Intramuscular Adipose Quality in Aging

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 65 Years – 80 Years
• Healthy volunteers: Accepted

Summary

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.

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.

Conditions

• Aging

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2026-04-15
• Primary completion: 2028-01-01
• Completion: 2028-01-01
• First posted: 2026-04-02
• Last updated: 2026-04-02

Locations

1 site across 1 country: United States