Physical Training May Reduce Muscle Aging and Insulin Resistance in People With Obesity

A new study published in Molecular Metabolism investigated the effects of physical training on cellular senescence (aging) in the skeletal muscle of people with obesity. The effects on insulin resistance, a process directly connected to cellular senescence, were also studied.

The study, conducted by Agnieszka Podraza-Farhanieh and colleagues at the University of Gothenburg in Sweden, enrolled 55 people divided into two groups. The first group included 23 young men with normal weight. The second group included 32 middle-aged people (20 men and 12 women) with obesity who did not have diabetes, inflammatory disease, or problems with substance abuse. The people with normal weight trained for 5 consecutive days for 4 weeks; exercise sessions included biking, running, and circuit training. The people with obesity trained for 6 months; exercise routines included endurance training on a treadmill, stepper, cross-trainer, rowing machine, and bicycle ergometer. Periods of warming up and cooling down were included in the training.

Muscle biopsy specimens were collected before and after the training intervention to examine markers that could identify cellular senescence and insulin sensitivity. Cell culture experiments were also conducted to evaluate how cellular senescence affects human satellite cells; essential genes were studied along with the molecular mechanisms behind insulin sensitivity.

Physical training reduced the levels of markers for cellular senescence, improved insulin sensitivity, and activated satellite cell responses in the skeletal muscle of both groups. The improvement in insulin sensitivity was linked to increased expression of glucose transporter type 4 (GLUT4) in the plasma membrane, facilitating better glucose uptake. The researchers also identified ZMAT3, a new marker of skeletal muscle senescence.

“One limitation of this study is that the lean and obese subject groups were not perfectly age-matched,” wrote the authors. The lean group’s average age was 27 years, while the obesity group’s average age was 49 years. Also, the two groups were not matched in terms of physical training duration. Protein expression profiles would have helped to identify chronic changes in essential genes related to cell senescence and insulin resistance but were not analyzed. “However, given the small sample size of biopsy material, we were unable to perform Western blot analyses,” added the authors.

The findings from this study highlight the importance of regular physical activity in a person’s lifestyle, reducing cellular senescence and enhancing insulin resistance in skeletal muscle, which helps to prevent metabolic disorders in people with obesity.

“Our findings provide a paradigm shift in the understanding of exercise as a direct modulator of SkM [skeletal muscle] senescence and metabolic health, both in young, lean individuals and in middle-aged individuals with obesity,” noted the authors. “Moreover, the identification of ZMAT3 as a novel senescence marker provides a potential valuable tool for future research and clinical applications aimed at targeting SkM [skeletal muscle] senescence to prevent age- and obesity-related metabolic diseases”, they concluded.

Podraza-Farhanieh A, et al. Mol Metab. 2025;95:102130. doi: 10.1016/j.molmet.2025.102130