Obesity-related fat cell signals shown to drive muscle loss in older adults

Researchers at the University of Birmingham have identified a new mechanism by which obesity may contribute to muscle loss in older adults, offering important insights into the condition known as sarcopenic obesity.

The study, published in the Journal of Cachexia, Sarcopenia and Muscle and delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) shows for the first time that extracellular vesicles — tiny particles released by fat tissue — can directly trigger muscle atrophy in human cells, providing new insight into how ageing and obesity interact to influence muscle loss.

Sarcopenic obesity, where excess body fat coexists with reduced muscle mass and strength, is an increasingly common condition in ageing populations and is associated with frailty, reduced mobility, and poorer overall health outcomes. It is estimated to affect around 11% of the population. 

In the study, researchers found that extracellular vesicles released from obese adipose (fat) tissue — but not lean tissue — caused significant thinning of muscle fibres derived from older adults. This effect was driven by specific molecular cargo carried within the vesicles, particularly miR-150-5p, a microRNA which influences gene expression pathways involved in muscle maintenance.

Crucially, the researchers found that muscle cells derived from younger adults were resilient to these effects. Exposure to obese adipose tissue and its extracellular vesicles did not trigger muscle thinning in younger muscle cells, highlighting an age-dependent vulnerability.

It isn’t just having more fat tissue that matters. Obesity changes how fat tissue behaves and how it communicates with muscle.

Dr Joshua Price, first author and postdoctoral researcher

Speaking about the findings of the study, Dr Joshua Price, first author and BRC-funded Postdoctoral Researcher within the Sarcopenia and Multimorbidity research theme, said: “It isn’t just having more fat tissue that matters. Obesity changes how fat tissue behaves and how it communicates with muscle. Ageing muscle is far more vulnerable to these altered signals, which helps explain why muscle loss accelerates with obesity later in life.”

The study identified this microRNA as a potential future therapeutic target, as inhibiting it could partly alleviate the muscle-wasting effect. The cumulative findings show that younger muscle has a protective resilience, whereas older muscle is made more vulnerable to the inflammatory and metabolic signals associated with obesity.

Through this research, we’ve identified a key molecular pathway by which obesity can accelerate muscle loss in older adults…This reinforces the importance of maintaining a healthy weight and muscle health as we age.

Professor Simon Jones, Professor in Musculoskeletal Ageing

Professor Simon Jones, senior author of the study, Professor in Musculoskeletal Ageing at the University of Birmingham and lead for the NIHR Birmingham BRC’s Sarcopenia and Multimorbidity research theme, said: “Through this research, we’ve identified a key molecular pathway by which obesity can accelerate muscle loss in older adults. Importantly, we found that younger muscle appears resilient to these harmful signals, whereas ageing muscle becomes more vulnerable. This reinforces the importance of maintaining a healthy weight and muscle health as we age.”

“Our findings also open two potential therapeutic avenues: either blocking or modifying the harmful extracellular vesicles released from obese tissue, or developing strategies to make older muscle more resilient, mimicking the protective effects seen in younger muscle.”