It’s no secret that a frustrating aspect of getting older is the facility to gain and hold onto some extra pounds, and poor diet and lack of sufficient exercise are not as much responsible as once thought, according to a new study. A team of scientists identified an enzyme — DNA protein kinase (DNA-PK) – that increases with age may be the culprit.
In a study, mice were given a high-fat diet and divided into two groups; one group had DNA-PK blocked while others did not. The group that had the enzyme blocked gained less weight than mice in the normal group.
It has been said that the average American adult gains approximately 30 pounds between ages 20 and 50, despite maintaining the same diet and lifestyle. Although this study was performed on mice and is not conclusively shown to be exactly the same in humans, the human body also manufactures DNA-PK, and there is compelling evidence to see if inhibiting this enzyme can indeed lead to weight loss during a phase of lifestyle renovation that includes nutrient-dense diet and moderate but regular exercise.
In the study, the mice that received the drug to block the DNA-PK also showed more mitochondria in skeletal muscle cells and corresponding increased aerobic fitness compared to the control mice.
In the abstract of the study published in the May 2017 issue of Cell Metabolism, (Vol. 25, No. 5, 1135-1146-e7, 2) the authors write, “hallmarks of aging that negatively impact health include weight gain and reduced physical fitness, which can increase insulin resistance and risk for many diseases, including type 2 diabetes. The underlying mechanism(s) for these phenomena is poorly understood. Here we report that aging activates DNA-dependent protein kinase (DNA-PK) in skeletal muscle, which suppresses mitochondrial function, energy metabolism, and physical fitness.”
They also describe the mechanism of action as follows: “DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism. Decreasing DNA-PK activity increases AMPK activity and prevents weight gain, decline of mitochondrial function, and decline of physical fitness in middle-aged mice and protects against type 2 diabetes. In conclusion, DNA-PK is one of the drivers of the metabolic and fitness decline during aging, and therefore DNA-PK inhibitors may have therapeutic potential in obesity and low exercise capacity.”