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!
Credit: Karen Laubenstein (Big Game Alaska)/U.S. Fish and Wildlife Service
When bears, bats, and other animals prepare to hibernate, they pack on fat at an impressive pace to almost double their weight. As they drift off into their winter slumber, their heart rates, breathing, and metabolism slow dramatically. Hibernating mammals can survive in this state of torpor for a period of weeks or even months without eating or drinking anything at all!
It’s a fascinating and still rather mysterious process—and one that William Israelsen of The University of Texas Southwestern Medical Center, Dallas, thinks may yield intriguing insights with implications for human health. A recipient of a 2015 NIH Director’s Early Independence Award, Israelsen plans to use a little-known mouse species to study hibernation in the laboratory at a level of detail that’s not possible in the wild. He especially wants to learn how hibernating animals shift their metabolic gears over the course of the year, and what those findings might reveal about human obesity, cancer, and other health conditions.
Today, we hear a great deal about which foods to eat and which to avoid to maintain a healthy body. Though we know that one of the strongest contributors to body weight is heredity, there has been less specific information available about the genetics underlying obesity. But research in this area is progressing at a phenomenal pace, and new genomic discoveries are helping to bring into better focus how our bodies store fat and how the complex interplay of genetics, diet, behavior, and other factors determine whether we can readily maintain a healthy body weight, or whether it takes a lot of work to do so.
Two papers in Nature provide lots of fresh clues into the genetic factors involved in predisposing to obesity. Researchers in the international Genetic Investigation of ANthropometric Traits (GIANT) Consortium, more than 500 strong and including some of the members of my own NIH research lab (including me), examined the genomes of more than half a million people to look for genes and regions of chromosomes that play a role in body fat distribution and obesity. They turned up over 140 genetic locations that, like low-intensity voices in a choir of many, contribute to these traits. Further analyses of the specific genes located in these regions suggest the possibility that the programming behind how fat cells form may influence their distribution, a discovery that could lead to exploitable findings down the road.