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Mice Who Feel Less Pain Also Live Longer, Burn More Calories

1017 Mice Who Feel Less Pain Also Live Longer, Burn More Calories
A youthful 30-month-old mouse navigates a maze during memory and learning tests. This and other mice lacking capsaicin pain receptors live longer and retain a more youthful metabolism / Celine Riera
By blocking a pain receptor in mice, researchers have actually extended their lifespans and rejuvenated them with the metabolism of a much younger mouse, a new study shows. Having a youthful, improved insulin response allowed older mice to deal better with high blood sugar levels.
The TRPV1 pain receptor is found in skin, nerves, and joints, and it reacts to extremely high temperatures and painful stimuli. TRPV1 also triggers the release of substances from the pancreas -- including a protein called CGRP -- which cause inflammation and prevent insulin release. Insulin helps with the uptake of sugar from the blood and the subsequent storage in tissues like fat. When CGRP blocks insulin release, blood glucose levels increase. 
“We think that blocking this pain receptor and pathway could be very, very useful not only for relieving pain, but for improving lifespan and metabolic health, and in particular for treating diabetes and obesity in humans,” says Andrew Dillin of the University of California, Berkeley. “As humans age they report a higher incidence of pain, suggesting that pain might drive the aging process.”
But too much stimulation is bad. Capsaicin, the thing that makes chili peppers hot, is known to activate TRPV1. Constant over-activation of TRPV1 on a nerve cell ends up killing the neuron that transmits signals from TRPV1 -- which mimics the loss of the pain receptor. This might explain why people on capsaicin-rich diets seem to have lower incidence of diabetes and metabolic problems; additionally, previous research showed that mice lacking TRPV1 are protected against diet-induced obesity. There's also an anti-migraine drug on the market that inhibits CGRP activity, producing a similar effect to that caused by blocking TRPV1. 
Dillin and colleagues showed that genetically manipulated mice lacking TRPV1 lived four months longer on average than normal mice. That’s about 14 percent longer: 12 percent for males and 16 percent for females. With lowered levels of CGRP, the TRPV1-deficient mice also showed signs of a youthful metabolism late in life; they quickly cleared sugar from the blood and seemed to burn more calories without having to exercise more. Similarly, giving the anti-migraine drug to older mice restored their metabolic health to that of younger mice. 
“Pharmacological manipulation of TRPV1 and CGRP may improve metabolic health and longevity,” Dillin explains in a news release. But what I really want to know: Is eating spicy foods the secret to a long, painless life? Maybe, Dillin tells Science, but you’d have to eat a lot of them over a long period of time. 
On the other hand, he explains to New Scientist: “Pain is very important for animals living in the wild and probably outweighs the benefits of a youthful metabolism.”
The work was published in Cell this week. 
Image: Celine Riera via UC Berkeley 


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