Pain-free people don’t age? Aging brings aches and pains: backaches, eye strain, sore joints, and more. But pain itself also appears to accelerate aging. Many studies have shown that people with chronic pain live shorter lives than others. But does this link between pain and aging appear by disease and decay along with it, or is it because people feel the sensation of pain itself? “If you burn your finger right now, does it affect your aging process?” Celine Riera asks, a postdoc from Andrew Dillin’s lab at the University of California, Berkeley. The answer is yes, according to a recent study Riera published in the journal Cell on mice. Riera’s study targeted mice genetically modified to lack the TRPV1 pain receptor. This pain receptor binds capsaicin, the same molecule inside chili peppers that makes you feel spicy. . In 2008, the researchers found that these mouse mutants were more metabolically active: after eating high-calorie foods, they gained far less weight than regular mice. “We showed that these animals have a greater capacity for energy expenditure.” Says Gerald Erne, a physiologist from the University of Georgia who led the study. After eating high-calorie food, mice without pain receptors (right) are slimmer than regular mice Considering the strong link between metabolism and aging, Riera and her colleagues decided to follow up on the lifespan of these mutant mice. They found that these mice lived an average of 100 to 130 days longer than regular lab mice, or a 12 to 16 percent increase in lifespan. In addition, the mutant mice showed “youthful” metabolic markers, including higher energy expenditure, oxygen consumption, and activity levels, even in their later years. So how could pain receptors affect metabolism? It turns out that in normal animals these pain receptors are located near the beta cells of the pancreas, which secrete insulin. When TRPV1 receptors are triggered by pain, they secrete a protein called calcitronin gene-related peptide (CGRP), which in turn prevents the pancreas from releasing insulin and causes inflammation. Aging mice “secrete too many kinds of CGRP,” Riera explains. “This causes a whole wave of metabolic and immune problems.” The study shows that mice without pain receptors don’t have this excess CGRP activity, which appears to be why they are metabolically healthier and live longer than the average mouse. CGRP is a fascinating protein. Naked mole rats can live up to 30 years longer than their rodent relatives without the CGRP protein inside their sensory nerves. Researchers have reported in the past that CGRP protein levels are higher in people with migraines and joint disorders. Because of this link to migraines, many drugs in the research phase target CGRP. this new study suggests that these drugs may have an effect on aging as well. “It’s so exciting that this pathway looks so easily modulated by pharmacologic means.” Riera said. (Interestingly, directly targeting the TRPV1 receptor, however, doesn’t seem to work. Many experimental-stage drugs targeting chronic pain take aim at this protein. But patients in clinical trials don’t just lose their pain sensation, they lose their ability to regulate their body temperature. “As a result, they either got heat stroke or scalded themselves in the shower.” Ern says, “These drugs work a little too well.”) Much remains to be confirmed about the TRPV1/CGRP channel and how it affects metabolism. Granted, this new study shows that getting rid of these pain receptors can boost metabolism, yet other studies have shown that stimulating these receptors-that is, eating spicy foods-has the same effect. “So these data seem a little inconsistent.” Ern says. Perhaps it’s because these proteins play different roles inside different tissues. “This new study is one of a myriad of studies in recent years on the relationship between sensory systems and longevity.” Joy Alcedo, a neurobiologist from Wayne State University, noted that he was not involved in the study. For example, in 2004 Alcedo’s research showed that in nematodes, certain taste neurons promote longevity while others inhibit it – likely also through insulin signaling. This study also found that neurons in the olfactory system also affect the lifespan of worms by regulating their reproductive system. And more recently, another study found that fruit flies that couldn’t taste water lived 43 percent longer than regular fruit flies. Considering the variety of environmental factors that affect an animal’s lifespan, Ossedo says, “I wouldn’t be surprised if more types of perceptual receptors that can affect lifespan are discovered.”