Chronic pain in humans is associated with worse health and a shorter lifespan, but the molecular mechanisms underlying these clinical observations have not been clear. A study published by Cell Press in the journal Cell reveals that the activity of a pain receptor called TRPV1 regulates lifespan and metabolic health in mice. The study suggests that pain perception can affect the aging process and reveals novel strategies that could improve metabolic health and longevity in humans.
"The TRPV1 receptor is a major drug target with many known drugs in the clinic that can affect its function," says senior study author Andrew Dillin of the University of California, Berkeley. "Finding that manipulation of this receptor can not only promote a youthful metabolism but also increase lifespan should be highly significant for age-related maladies, diabetes being a major one."
Past research has shown that mice lacking TRPV1 are protected against diet-induced obesity, suggesting that this receptor plays a role in metabolism. Intriguingly, diets rich in capsaicin - the active molecule of chili peppers that can overstimulate and kill TRPV1 neurons - have long been linked to lower incidents of diabetes and metabolic problems in humans. Moreover, disruption of sensory perception increases longevity in worms and flies. But until now, it was not known whether sensory perception also affects aging in mammals.
Addressing this question in the new study, Dillin and his team found that mice genetically manipulated to lack TRPV1 receptors lived on average nearly four months, or about 14%, longer than normal mice. The TRPV1-deficient mice also showed signs of a youthful metabolism late in life, due to low levels of calcitonin gene-related peptide (CGRP) - a molecule that increases blood glucose levels and thus could contribute to the development of type 2 diabetes. Throughout aging, these mice showed improved glucose tolerance - the ability to quickly clear sugar from the blood - as well as signs that they could burn more calories without exercising more than normal.
Moreover, old mice treated with a compound that inhibits the activity of CGRP receptors showed a more youthful metabolic profile than untreated old mice. "Our findings suggest that pharmacological manipulation of TRPV1 and CGRP may improve metabolic health and longevity," Dillin says. "Alternatively, chronic ingestion of compounds that affect TRPV1 such as capsaicin might help prevent metabolic decline with age and lead to increased longevity in humans."