Blocking Pain Receptors Extends Lifespan, Mouse Study Suggests

Scientists have found a way to beat back the hands of time and fight the ravages of old age, at least in mice. A new study finds that mice bred without a specific pain sensor, or receptor, live longer and are less likely to develop diseases such as diabetes in old age. What’s more, exposure to a molecule found in chili peppers and other spicy foods may confer the same benefits as losing this pain receptor—meaning that humans could potentially benefit, too.

When you touch something hot or get a nasty paper cut, pain receptors in your skin are activated, causing neurons to relay a message to your brain: “Ouch!” Although pain protects your body from damage, it also causes harm. People who experience chronic pain, for example, are more likely to have shorter lifespans, but the reason for this has remained unclear.

To investigate further, researchers from the University of California (UC), Berkeley, bred mice without a pain receptor called TRPV1. Found in the skin, nerves, and joints, it’s known to be activated by the spicy compound found in chili peppers, known as capsaicin. (When you feel like your mouth is burning after eating a jalapeño, that’s TRPV1 at work.) Surprisingly, the mice without TRPV1 lived on average 14% longer than their normal counterparts, the team reports today in Cell. (Meanwhile, calorie restriction—another popular way of lengthening mouse lifespans—can make them live up to 40% longer.) When the TRPV1-less mice got old, they still showed signs of fast, youthful metabolisms. Their bodies continued to quickly clear sugar from the blood—a trait called glucose tolerance that usually declines with age—and they burned more calories during exercise than regular elderly mice. 

The reason for the mice's increased longevity may lie in the TRPV1 receptor's role in regulating insulin, a hormone that removes sugar from the blood, says lead researcher Andrew Dillin, a molecular biologist at UC Berkeley. In the pancreas, TRPV1 neurons stimulate the release of a substance called CGRP, which prevents insulin from entering the bloodstream. With less insulin, it’s harder to control blood sugar. Mice without the TRPV1 gene had low levels of CGRP, which meant that they had more insulin, explaining their enhanced ability to manage glucose levels. Interestingly, the extremely long-lived naked mole rat, which lives more than 30 years, naturally lacks CGRP, suggesting a key role for this chemical in the aging process, according to Dillin.

TRPV1 is already a popular target for drug companies trying to treat pain, and a therapy that blocks CGRP is now in development for migraines. But Dillin suggests that companies should think beyond pain control. “These drugs might also be useful for treating diabetes and obesity,” he says. Already, diets rich in capsaicin have been linked to lower incidences of diabetes and metabolic problems in humans, he notes. So might spicy foods be a way of extending life? Maybe, Dillin says, but you’d have to eat a lot of them over a long period of time. “Prolonged exposure to capsaicin can actually kill the neuron” that transmits signals from TRPV1, he explains. Knocking out those signals might mimic the effects of being born without TRPV1 in the first place and, therefore, could lead to a longer life.

The idea that pain could cause aging is an intriguing one, says molecular biologist David Sinclair of Harvard Medical School in Boston, who was not involved in the study. “It is striking that the mice without TRPV1 were protected from some of the ravages of old age, including declines in metabolism, cognition, and physical activity,” Sinclair says. While there's no guarantee that pain receptors control aging in humans, he notes, perhaps the next step could be “to see if people with different variations of the CGRP gene are protected from age-related diseases.”

Original article:

This story has been provided by AAAS, the non-profit science society, and its international journal, Science.



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