Scientists have uncovered an enzyme that is crucial to understanding why exercise is beneficial to our health. Importantly, this discovery has opened the door to the development of drugs that boost the activity of this enzyme, thereby protecting against its negative effects.

Scientists at Monash University in Australia have uncovered an enzyme that plays a critical role in why exercise improves our health. Importantly, this discovery has paved the way for drugs that boost the activity of this enzyme, protecting against the effects of aging on metabolic health, such as type 2 diabetes.

In the next three decades, the number of individuals aged 60 and above will triple globally, with more than six million Australians aged 65 and up by 2031. Since the frequency of type 2 diabetes rises with age, the disease will become more prevalent worldwide as the population ages.

Insulin resistance, or the body’s inability to respond to insulin, is one of the key causes for the increased prevalence of type 2 diabetes with age, and this is generally caused by decreased physical activity as we age.

The exact mechanisms by which physical inactivity promotes the development of insulin resistance, however, remain unknown.

Now, Monash University researchers in Australia have identified how physical activity improves insulin responsiveness, which in turn improves metabolic health. Importantly, the enzymes they uncovered that are important in this pathway could be targeted by medications to guard against age-related problems including muscle wasting and diabetes.

Professor Tony Tiganis’ research team at Monash University’s Biomedicine Discovery Institute (BDI) discovered that reductions in skeletal muscle reactive oxygen species (ROS) formation during ageing play a key role in the development of insulin resistance. According to Professor Tiganis, skeletal muscle creates reactive oxygen species (ROS) on a continuous basis, which increases during physical activity.

“Exercise-induced ROS drives adaptive responses that are integral to the health-promoting effects of exercise,” he said. 

In a paper published today in the journal Science Advances, the research team shows how an enzyme called NOX-4 is important for exercise-induced ROS and the metabolic health that comes with it. This enzyme is called NOX-4.

The researchers discovered that following exercise, NOX4 levels in skeletal muscle rise, which leads to an increase in ROS, which triggers adaptive responses that protect mice from developing insulin resistance, which would otherwise occur with age or diet-induced obesity.

Importantly, the researchers discovered that NOX4 levels in skeletal muscle are linked to an age-related reduction in insulin sensitivity.

“In this study we have shown, in animal models, that skeletal muscle NOX 4 abundance is decreased with ageing and that this leads to a reduction in insulin sensitivity,” added Professor Tiganis.

“Triggering the activation of the adaptive mechanisms orchestrated by NOX4  with drugs, might ameliorate key aspects of ageing, including the development of insulin resistance and type 2 diabetes,” he said. 

“One of these compounds is found naturally, for instance, in cruciferous vegetables, such as broccoli or cauliflower, though the amount needed for anti-ageing effects might be more than many would be willing to consume.” 

Source: 10.1126/sciadv.abl4988

Image Credit: iStock

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