Biologists from the Salk Institute, who were led by Professor Andrew Dillin (a Howard Hughes faculty member who also has joint appointments at UC Berkeley and Glen Center for Aging Research) found that removing a pain receptor in mice has the trifecta effect of lengthening life span, improving cognition, and protecting them against obesity.
This effect had been seen before in roundworms and flies but as mice are mammals like us these new results showed that the pain receptor in humans might be a control knob biologically relevant in humans. A summary of the effects is given by the researchers:
- Mutation of pain receptor extends lifespan in mice and worms
- The pain receptor has an impact on insulin secretion, thereby alters metabolism to make mice healthier
- The mice with mutations in the pain receptor grow normally but have youthful metabolism even when old
- Using a chemical to block the downstream effect of the pain receptor also increases metabolic health at old age
Judging from the “survival curves” which show the survival of a population of mice over time, normal mice lived about 30 months in the study whereas the specially engineered mice lacking the pain receptor lived about 33 months, a 10% effect.
Previously, in 2007 UCSF scientists headed by Professor Cynthia Kenyon, and Baylor scientists led by Professor Scott Baylor, found that mutations in the analogous pain receptor lengthened the life spans of two very distantly related organisms: roundworms (C elegans) and flies (D melanogaster).
The fact that the effect was duplicated and verified in two organisms presaged the new study that showed the same relationship between longevity and the receptor.
Specifically, Dillin found that the pain receptor TRPV1, when active, sends molecular messages to the nucleus of cells which tells them to churn out proteins many of involving metabolism. Key proteins affected are calcineurin, CRTC1 and the transcription factor CREB. In particular, CREB itself was identified as a longevity controller in another earlier study therefore the significance of Dillin’s work is a more “upstream” or “master” regulator was discovered.
The mice are not without side effects. Without the receptor they areless responsive to pain and stimuli that precede pain (such as strong pressure or near painful levels of heat).
The same receptor is also the one that binds capsaicin, the chemical responsible for sensations of spiciness. Therefore these mice, were they to be tested, would likely to be found less sensitive to spicy food.
On a more practical level, the work is notable for uncovering yet another mechanism that controls lifespan. It is probably unwise to genetically engineer out any of the pain receptor genes as sensation to pain is a powerful survival sensory mechanism.
Instead scientists may want to design drugs that block the signals being sent to the metabolic pathways that are linked to aging, thereby finding a “drug-like” strategy to mimick the same effect as removing the gene.
The research was published in Cell.