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In the Beat of a Heart: Life, Energy, and the Unity of Nature
It now looks as though it’s not how quickly you burn energy that influences the aging process but the way that you burn it. Long-lived mice do not simply have faster metabolisms than their shorter-lived counterparts. They also have different mitochondrial chemistry. Mitochondria can do two things with food: turn it into cellular fuel, in the form of ATP, or burn it off as heat. The chemical reactions that turn food into heat produce fewer free radicals than those that produce ATP. Cells have proteins that switch their mitochondria from ATP mode into heat mode, a process called mitochondrial uncoupling. The long-lived, energy-hungry mice in the Aberdeen experiment had a higher level of this uncoupling. Humans use mitochondrial uncoupling to keep warm. Babies have a tissue called brown fat that is stuffed with mitochondria and with proteins that uncouple them, and which disappears around the age of one. And the indigenous people of cold climates have more mitochondrial uncoupling than temperate or tropical groups. This might be part of the reason why cold dwellers have lower rates of neurodegenerative disorders, such as Alzheimer’s, but are more prone to diseases of energy metabolism.
Some researchers, including Speakman, are on the trail of drugs that might increase life span by uncoupling mitochondria. We already know some chemicals that do that, but they tend to have unfortunate side effects. One such compound is 2,4-dinitrophenol. Found in explosives and insecticides, this chemical’s metabolic properties were discovered during the First World War, when workers exposed to dinitrophenol in munitions factories began losing weight at startling rates—because their metabolic rates had shot up. Dinitrophenol was sold as a slimming drug in the 1930s but was later banned because an overdose makes the body cook itself. Some bodybuilders still use it as a means of crash dieting, and some have died from it. Another chemical that uncouples mitochondria is Ecstasy, or MDMA, which often causes an unpleasant and potentially dangerous rise in body temperature. The drug produces this effect by activating uncoupling proteins in the cells. Together, this evidence raises the thrilling prospect of a pill that makes you thin, high, and ageless, if rather flushed and sweaty.