26 May 2014

Blocking the pain receptor prolongs life

It is well known that aging is accompanied by various painful manifestations. At the same time, the results of a study conducted by scientists at the University of California at Berkeley, working under the guidance of Dr. Andrew Dillin, indicate that the pain receptor, in turn, contributes to the development of metabolic disorders and aging.

Earlier studies revealed a correlation between chronic pain syndrome and short human life expectancy. The relationship between the pain receptor TRPV1 (transient receptor potential cation channel subfamily V member 1) and metabolism was also demonstrated, including the fact that mice without this receptor are more likely to develop obesity when eating fat-rich food.

In experiments on transgenic mice, Dillin and his colleagues found that the absence of the TRPV1 receptor increases the life expectancy of males by 12% and females by 16% compared to control group animals.

In search of an explanation for this phenomenon, they found that even at a very old age, the body of experimental animals reacted very effectively to glucose. In normal young mice with a good metabolism, glucose is rapidly excreted from the bloodstream, whereas in aging animals with metabolic disorders, this process slows down. At the same time, the body of mice without the TRPV1 receptor retained the ability to burst insulin secretion and rapid glucose utilization throughout their lives.

In order to understand how TRPV1 affects insulin synthesis, the authors conducted experiments on another model organism – roundworms Caenorhabditis elegans. The loss of the equivalent of the TRPV1 receptor increased the lifespan of nematodes by 32% compared to the control group.

When conducting experiments on C.elegans and mice, the researchers found that excessive TRPV1 activity negatively affects life expectancy by disrupting the signaling cascade mediated by calcium ions. In mice, this eventually leads to hyperproduction by sensitive neurons innervating the pancreas of a neuropeptide known as the Calcitonin Gene-Related peptide (CGRP). As a result, insulin secretion is suppressed.

To obtain final confirmation of the revealed pattern, scientists blocked the synthesis of the calcitonin peptide gene in old wild-type mice. After some time, the metabolism of animals began to approach the metabolism of young individuals in terms of efficiency.

A diagram from an article in Cell.

The authors suggest that hyperactivation of CGRP in old animals is the result of chronic inflammation. It is known that the inflammatory status activates pain receptors and always accompanies type 2 diabetes mellitus.

Pharmaceutical companies have already attempted to develop drugs to relieve chronic pain by suppressing CGRP activity. However, patients taking antagonists of this receptor often ignored the feeling of heat, which led to the development of life-threatening hyperthermia and the termination of clinical studies. The authors believe that the use of alternative approaches will allow the development of safe drugs to affect CGRP.

Currently, a drug that affects CGRP for the treatment of migraine is under development. However, Dillin notes that, unlike drugs for the relief of acute pain, drugs for the treatment of chronic diseases, such as metabolic disorders, should be suitable for long-term use. To date, it is unclear how safe it is for a person to permanently inhibit pain receptors.

Article by C.E. Riera et al. TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling is published in the journal Cell.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: No Pain, Big Gain.


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