The struggle to maintain a healthy weight is a lifelong challenge for many of us. In fact, the average American packs on an extra 30 pounds from early adulthood to age 50. What’s responsible for this tendency toward middle-age spread? For most of us, too many calories and too little exercise definitely play a role. But now comes word that another reason may lie in a strong—and previously unknown—biochemical mechanism related to the normal aging process.
An NIH-led team recently discovered that the normal process of aging causes levels of an enzyme called DNA-PK to rise in animals as they approach middle age. While the enzyme is known for its role in DNA repair, their studies show it also slows down metabolism, making it more difficult to burn fat. To see if reducing DNA-PK levels might rev up the metabolism, the researchers turned to middle-aged mice. They found that a drug-like compound that blocked DNA-PK activity cut weight gain in the mice by a whopping 40 percent!
Jay H. Chung, an intramural researcher with NIH’s National Heart, Lung, and Blood Institute, had always wondered why many middle-aged people and animals gain weight even when they eat less. To explain this paradox, his team looked to biochemical changes in the skeletal muscles of middle-aged mice and rhesus macaques, whose stage in life would be roughly equivalent to a 45-year-old person.
Their studies, published recently in Cell Metabolism, uncovered evidence in both species that DNA-PK increases in skeletal muscle with age . The discovery proved intriguing because the enzyme’s role in aging was completely unknown.
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