Enzyme activated by exercise presents new target for anti-aging drugs
Regular exercise is generally a good idea at any age, but maintaining an active lifestyle is especially important as we get older. Scientists in Australia have shed further light on the reasons why, implicating a new enzyme produced through exercise that helps stave off declining metabolic health – a discovery that offers new target for potential drugs that protect against consequences of aging.
Carried out by scientists at Monash University in Melbourne, the study was designed to drill into one of the effects of physical inactivity among older people; the development of insulin resistance. This means the body's cells don't respond well to insulin and don't take up glucose as they should, leaving it to build up in the blood instead. Insulin resistance is associated with obesity and is a major risk factor for type 2 diabetes, and the authors sought to unearth some of the biological mechanisms linking it to reduced physical activity in aging populations.
The scientists were able to show that physical activity promotes metabolic health via the production of reactive oxygen species (ROS) in skeletal muscle. ROS is produced in skeletal muscle as a matter of course, but it declines with age, which the researchers say helps drive the development of insulin resistance.
Through experiments on mice, the scientists showed a newly discovered enzyme called NOX4 to be at the center of this process. Levels of the enzyme were heightened after exercise, which in turn boosted levels of ROS and protected the mice from developing insulin resistance. This was true of aging mice and mice with diet-induced obesity.
“Exercise-induced ROS drives adaptive responses that are integral to the health-promoting effects of exercise,” says study leader Professor Tony Tiganis.
The experiments also showed that concentrations of NOX4 in skeletal muscle are directly related to aging and a decline in insulin sensitivity. This has some parallels to research published last month demonstrating how a plant extract could counter insulin resistance by mimicking a growth factor in skeletal muscle that declines in obese subjects.
Similarly, the authors of this new study say NOX4 has the potential to be targeted with drugs that boost its activity and maintain metabolic health in aging people. They also imagine that the solution could be found in nature, though there will be much work to do before this can be translated into therapeutics.
“Triggering the activation of the adaptive mechanisms orchestrated by NOX4 with drugs, might ameliorate key aspects of aging, including the development of insulin resistance and type 2 diabetes," says Tiganis. "One of these compounds is found naturally, for instance, in cruciferous vegetables, such as broccoli or cauliflower, though the amount needed for anti-aging effects might be more than many would be willing to consume.”
The research was published in the journal Science Advances.
Source: Monash University