Sex Differences in Muscle Fat Offer Clues for Age-Related Disease Treatments

Researchers at UT Southwestern Medical Center have discovered sex-specific differences in how fat accumulates in muscle and bone, uncovering patterns that could inform new approaches to treating age-related diseases. Their findings, published in Diagnostics, detail how fat infiltrates skeletal muscle and accumulates in subcutaneous tissue and bone marrow, revealing key differences between men and women shaped by age and body mass index (BMI).

“Musculoskeletal disorders are the leading cause of disability in the U.S., with enormous impacts on quality of life and longevity,” said senior author Jimin Ren, Ph.D., Associate Professor in the Advanced Imaging Research Center (AIRC) and of Radiology at UT Southwestern. “This study identifies key contributors to muscle fat infiltration (MFI), a harmful accumulation of fat within skeletal muscle that can lead to muscle atrophy and dystrophy.”

The study analyzed magnetic resonance imaging (MRI) scans from 107 UTSW patients, 64 males and 43 females ages 11 to 79, representing diverse ethnicities and a range of BMI. The team focused on the lower extremities, finding that MFI increased significantly with age in women but was more strongly correlated with body weight in men. Additionally, the average subcutaneous fat thickness was about twice as high in women (8.9 millimeters vs. 4.3 mm). This fat increased with age in women but decreased in men, especially among nonobese individuals.

The researchers also observed a relationship between MFI and bone marrow cross-sectional area (BMA), highlighting the interdependence of muscle and skeletal health. Weakened bone structure may facilitate fat infiltration into surrounding muscles, creating physical challenges that increase risks for falls, fractures, and metabolic disorders. These results suggest preserving overall musculoskeletal strength is essential for managing age-related conditions, particularly in older adults.

“Skeletal muscle is the body’s largest organ by mass and plays a critical role in regulating glucose metabolism,” Dr. Ren said. “When fat overly accumulates in muscle, it can impair the muscle’s ability to process glucose, which increases the risk of insulin resistance and associated health conditions like obesity, heart failure, stroke, sarcopenia, osteoporosis, chronic kidney disease, and Type 2 diabetes.”

The study sheds additional light on sex-specific health challenges as individuals age. For example, in women, hormonal changes after menopause likely amplify risks for conditions such as sarcopenia (age-related loss of muscle mass and strength) and osteoporosis (which weakens bones). In men, the stronger correlation between body weight and fat infiltration emphasizes the importance of managing obesity to protect muscle function.

Detailing how sex, age, and BMI shape fat distribution, the findings offer insights for developing personalized strategies – including exercise regimens, nutritional guidance, and therapies – to promote musculoskeletal health and prevent age-related decline. In addition, Dr. Ren said, the research holds promise for clinical care by highlighting markers such as subcutaneous fat thickness, intramuscular fat, and BMA, which could be used to screen and monitor muscle metabolic health and assess the risk of sarcopenia and osteoporosis noninvasively.

“By linking fat infiltration within muscle to fat in the bone marrow, the study highlights a potential avenue for dual-targeted therapies that support both muscle and bone,” said lead author Talon Johnson, Ph.D., a postdoctoral research fellow in the AIRC. “Such an integrated perspective on bone and muscle health could contribute to the development of early interventions for metabolic and musculoskeletal disorders that become more common with aging.” 

Reference: Johnson T, Su J, Andres J, Henning A, Ren J. Sex differences in fat distribution and muscle fat infiltration in the lower extremity: a retrospective diverse-ethnicity 7T MRI study in a research institute setting in the USA. Diagnostics. 2024;14(20):2260. doi: 10.3390/diagnostics14202260

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