Billions of people struggle with weight gain and obesity in the United States and across the globe. The Centers for Disease Control and Prevention (CDC) report that over a third of the U.S. population are obese, and the World Health Organization (WHO) estimate that almost 2 billion adults are overweight worldwide.Obesity can generally be prevented with a healthful diet and plenty of exercise, but sometimes we continue to gain weight despite our best efforts. For instance, people tend to gain weight as they age – particularly around the belly – and can subsequently become overweight, in a phenomenon commonly known as midlife weight gain.
In fact, it is estimated that the average U.S. adult gains 30 pounds between the ages of 20 and 50, despite the fact that people tend to eat less during this period.
This paradox sparked the interest of a team of researchers from the National Institutes of Health (NIH), who set out to investigate the mechanism behind midlife weight gain.
The researchers were led by Dr. Jay H. Chung, Ph.D., head of the Laboratory of Obesity and Aging Research at the National Heart, Lung, and Blood Institute, which is a part of the NIH.
The findings were published in the journal Cell Metabolism.
Specific enzyme inhibitor lowers weight gain by 40 percent
Chung and team investigated the biochemical transformations that take place in animals in their middle age. Looking at animals that were the equivalent of 45 human years old, Chung and team found that an enzyme – called DNA-dependent protein kinase (DNA-PK) – becomes more active with age.
Furthermore, the researchers found that DNA-PK turns nutrients into fat and lowers the number of mitochondria.
Mitochondria are the so-called powerhouses of the cells. They are small compartments inside the cell that turn food into energy and break down waste products. Mitochondria are responsible for producing as much as 90 percent of the energy that cells need to grow, and they also play a crucial role in the death of other cells.
The younger we are, the more mitochondria we have in our bodies. From midlife onward, however, the number of mitochondria starts to decrease. It is known that a lower number of mitochondria can lead to obesity, and mitochondrial dysfunction has been associated with a decrease in one’s ability to exercise.
To further understand the role of the DNA-PK enzyme, Chung and team tested its effect on two groups of mice. Both groups were fed a high-fat diet, but one group received an inhibitor that blocked the DNA-PK enzyme, while the other group did not.
The group that received the DNA-PK-inhibiting drug gained 40 percent less weight than those that did not receive the drug. Additionally, the drug increased aerobic fitness and decreased the rate of obesity and type 2 diabetes in obese, middle-aged mice.
Finally, the inhibitor also increased the number of mitochondria in the mice’s skeletal muscle.
Study may pave way for new type of weight loss medication
Given that obesity is a risk factor for so many chronic illnesses, the researchers suggest that their findings may help to lower the risk of conditions such as heart disease, cancer, and Alzheimer’s disease.
The study’s lead author comments on the findings:
“Our studies indicate that DNA-PK is one of the drivers of the metabolic and fitness decline that occurs during aging, which makes staying lean and physically fit difficult and increases susceptibility to metabolic diseases like diabetes. The identification of this new mechanism is very important for improving public health.”
Dr. Jay H. Chung
Although we are a long way from developing a similar DNA-PK inhibitor in humans, Dr. Chung suggests that the new study may pave the way for developing an innovative kind of weight loss medication. Dr. Chung also underscores how the study challenges the current societal perceptions around midlife weight gain.
“Our society attributes the weight gain and lack of exercise at midlife – approximately 30-60 years – primarily to poor lifestyle choices and lack of willpower, but this study shows that there is a genetic program driven by an overactive enzyme that promotes weight gain and loss of exercise capacity at midlife.”
Dr. Jay H. Chung
This should not discourage people from eating healthfully and exercising, however, adds Dr. Chung.
Learn how midlife obesity could accelerate brain aging by 10 years.