Genetic engineering of a mitochondrial gene in mice to generate more heat causes the mice to live longer.
By making the skeletal muscles of mice use energy less efficiently, researchers report in the December issue of Cell Metabolism, a publication of Cell Press, that they have delayed the animals’ deaths and their development of age-related diseases, including vascular disease, obesity, and one form of cancer. Those health benefits, driven by an increased metabolic rate, appear to come without any direct influence on the aging process itself, according to the researchers.
The mitochondria powering the mouse muscles were made inefficient by increasing the activity of so-called uncoupling protein 1 (UCP1). UCP1 disrupts the transfer of electrons from food to oxygen, a process known as mitochondrial respiration, which normally yields the energy transport molecule ATP. Instead, the energy is lost as heat.
“When you make the mitochondria inefficient, the muscles burn more calories,” a metabolic increase that could be at least a partial substitute for exercise, said Clay Semenkovich of Washington University School of Medicine in St. Louis. “There are a couple of ways to treat obesity and related diseases,” he continued. “You can eat less, but that’s unpopular, or you could eat what you want as these animals did and introduce an altered physiology. It’s a fundamentally different way of addressing the problem.”
This result suggests that the development of drugs to cause the same effect in humans might increase human longevity.
This genetic alteration produced many beneficial effects.
In the new study, Semenkovich’s group used these mice to determine whether respiratory uncoupling in skeletal muscle—a tissue that adapts to altered heat production and oxygen consumption during exercise—can affect age-related disease. They found that animals with increased UCP1 only in skeletal muscle lived longer. Altered female animals also developed lymphoma, a type of cancer that originates in white blood cells called lymphocytes, less frequently. In mice genetically predisposed to vascular disease, the increase in UCP1 led to a decline in atherosclerosis in animals fed a “western-type” high-fat diet. Likewise, mice predisposed to developing diabetes and hypertension were relieved of those ailments by increased UCP1 in skeletal muscle. The “uncoupled mice” also had less body fat (or adiposity) and higher body temperatures and metabolic rates, among other biochemical changes.
I would rather have a version of UCP1 that I could switch between different levels of efficiency. Before going on a hike or after an accident or natural disaster it might make sense to shift UCP1 into a more efficient form. Basically, burn off excess energy when you can afford to do so but put your body into a high efficiency mode of operation when the need arises.
The development of drugs that reduce appetite should eventually reduce the benefit of turning UCP1 into a less efficient form. No need to burn off excess sugars and fats if you can make your brain not crave calories in the first place.
|Share |||Randall Parker, 2007 December 04 11:57 PM Aging Genetics|