A new study from researchers in Australia looks at how age and decreased physical activity heightens the risks of type 2 diabetes and muscle wasting. The research group has isolated an enzyme that has been associated with exercise that could actually be the key to protecting people from insulin resistance. They hope that the same protective effect could be made possible through drugs that can activate this enzyme.
With the world population getting older every minute, the United Nations estimates that at least 1 in 6 people will be over the age of 65 by the year 2050.
As people age, the amount of physical activity that they do often decreases as well, and this play a key role in the increased risk of type 2 diabetes, as well as muscle wasting in those who are older in age.
While there are a number of studies that share the benefits of physical activity, which are much more well known as accepted, there isn’t much known about the way exercise aids in metabolic health or how insulin resistance is lessened with age as well.
How the Exercise-Related Enzyme Was Discovered
Appearing in the Science Advances, a recent study in mice looks at an exercise-related enzyme that could possibly aid in the prevention of oxidative damage that usually happens during the development of age-associated type 2 diabetes.
Known as NADPH oxidase 4 (NOX4), this enzyme’s levels in our skeletal muscles actually increase after we exercise. Easily explained, the skeletal muscles are those that are connected to the bones. When you exercise, you expose those muscles to stress, which increases the body’s tolerance for future stressors.
The reactive oxygen species (ROS) are generated in the muscles while we exercise. And as explained by the authors of the new study, they share that ROS “generated during exercise are considered integral for the health-promoting effects of exercise.”
Speaking with Medical News Today (MNT), lead study author Prof. Tony Tiganis from the Monash University Biomedicine Discovery Institute, in Clayton, Australia, talked about the early findings of how ‘a ROS called hydrogen peroxide enhanced insulin sensitivity in mice.’
For the new study, the research group focused on a deeper investigation on the relationship between exercise, ROS, and insulin resistance.
Prof. Tiganis explained, “Our findings provide insight into why and how exercise promotes insulin sensitivity and is beneficial for metabolic health.”
Finding How Aging Affects Production of Enzyme
Explained by the lead author, the new study found that ‘ROS generated by NOX4 after exercise activate an enzyme.’ Called NFE2L2, this enzyme creates “a robust antioxidant defense response.”
As shared by Prof. Tiganis, this response doesn’t necessarily affect insulin sensitivity immediately. But it lessens “mitochondrial oxidative stress and the oxidative damage of proteins and lipids that otherwise lead to the decline in insulin sensitivity and the development of insulin resistance over time.”
More research shows how ROS can damage cells through oxidative stress. Moreover, there is evidence that shows how oxidative stress also plays a role in the development of insulin resistance. This is why the body needs to deal with ROS as fast as possible.
As one exercises, ROS are produced in large amounts, which means that the body needs to find a way to clear them almost immediately. While exercise helps the body remove ROS faster, it then reduces the risk of any damage that can be caused by oxidative stress.
The study authors deduce, “In this study, we demonstrate that the generation of ROS by skeletal muscle NOX4 […] induces adaptive responses that prevent oxidative damage, maintain muscle function and exercise capacity, and attenuate the age – and obesity – associated development of insulin resistance.”
Notably, the researchers also pointed out how NOX4 levels naturally get reduced with age. So while the NOX4 levels decline over time, so do ROS levels. And as ROS production lowers, the body doesn’t benefit from the “adaptive responses” which help preserve insulin sensitivity.
Prof. Tiganis shared, “Whereas NOX4 expression in mice or humans is increased in skeletal muscles after exercise, its abundance declines with age, at least in mice, and this contributes to the development of insulin resistance.”
MNT also spoke with assistant professor of clinical medicine and medical director of inpatient diabetes at Indiana University’s Adult Academic Health Center, Dr. Swapnil Khare, to ask about her reaction to the study.
She said, “With aging and obesity, there are more problems with insulin resistance, glucose metabolism, and type 2 diabetes. This is a very relevant study. We know we need a balance between the oxidative species in our bodies. Exercise helps that. Now we have a better picture of how it helps.”
More Research Needed
Dr. Khare further notes that although it’s incredibly important to promote healthy lifestyles and exercise, there are still those that are not able to because of certain physical limitations and other particular factors. She also notes that any further studies on this topic will focus on those types of individuals.
Moreover, the study authors also share that there is a need for more research that looks into the beneficial effects of NOX4 in humans.
“If our findings in mice translate to humans, such compounds and approaches may be useful for combatting the development of insulin resistance, and thereby type 2 diabetes, in aging and increasingly sedentary people,” added Prof. Tiganis
He concluded, “Our next goal is to determine if skeletal muscle NOX4 also declines in aging humans and whether this is accompanied by diminished antioxidant defense and insulin resistance.”
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