Longevity Briefs: Could This Drug Prevent Muscle Loss And Obesity In Old Age?

Posted on 8 April 2022

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Sarcopenic obesity is a new class of obesity occurring mainly in older adults, and in which muscle mass is low while fat (adipose tissue) is high. This is a deadly combination that results in poor quality of life, increased risk of age-related diseases, and for which medical interventions are ineffective. Research suggests that faulty mitochondria, the ‘cellular organs’ responsible for converting nutrients into a form of energy that the cell can use, play a central role in sarcopenic obesity. Could drugs targeting the mitochondria allow us to reverse or prevent this disease in older adults?

What did the researchers do: In this study, researchers fed 12 mice a high fat diet so that they would develop sarcopenic obesity. When the mice were 80 weeks old (this is roughly equivalent to a 60 year old human), they were randomly assigned to either serve as a control or receive an oral drug called BAM15. BAM15 is a compound that causes the mitochondria to ‘spin their wheels’ by switching to a very inefficient mode of energy production, a process known as mitochondrial uncoupling. While this might sound like a bad thing, mitochondrial uncoupling has been shown to improve mitochondrial health and extend lifespan in mice. Here, researchers wanted to see what effects it would have on obesity and sarcopenia.

Details are in the caption following the image
This is the working model of how mitochondrial dysfunction leads to sarcopenia, and how BAM15 prevents this. In old age and obesity, mitochondria become damaged and release a protein called cytochrome C. This activates the cell’s self destruct system (apoptosis) and leads to increased degradation of muscle proteins and reduced muscle mass and strength. BAM15 prevents this by improving mitochondrial health, eliminating damaged mitochondrial and promoting the production of new mitochondria.
Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control

Key takeaway(s) from this research: Despite continuing to consume a high-fat diet, mice receiving BAM15 increased their daily energy expenditure and lost over 20% of their body fat in the 10 weeks following the start of treatment, while their muscle mass increased by 8% and their muscle strength increased by 40%. As expected, the control mice continued to gain fat mass. BAM15 also reduced muscle inflammation and improved the quality control of mitochondria (in which faulty mitochondria are destroyed), two probable mechanisms through which muscle function was improved.

Loss of fat mass is usually accompanied by some degree muscle loss, so the fact that mice taking BAM15 gained muscle is very impressive, and suggests that BAM15 and other mitochondrial uncouplers might be very promising drugs for treating sarcopenic obesity and improving health in old age more generally. We should temper our expectations, however, as this study was still very small, and comes with all the usual caveats of animal studies. Findings in mice may not translate to humans, the mice used here are genetically susceptible to obesity, and aren’t representative of a genetically diverse human population.


Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control: https://doi.org/10.1002/jcsm.12982

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