A new paper in Cell shows a fascinating link between sensing pain and longevity. TRPV1, more commonly known as the capsaicin receptor, is expressed on our sensory neurons and is important for detecting pain and heat.

When mice were engineered to lack this receptor (knock-outs), they surprisingly also lived longer. Males lived on average 11.9% longer, while females experienced a 15.9% extension. (Note: both normal and knock-out males have a longer lifespan than female mice.) When the researchers probed why the mice were living longer, they found significant differences in the metabolism of the mice. When normal mice age, they experience a drop in their metabolism, as measured by a loss of cycling of the respiratory exchange rate and a decrease in glucose tolerance. In contrast, the pain receptor deficient mice maintained high metabolism rates similar to young mice, and were able to secrete higher levels of insulin.

What's the connection between a pain receptor and metabolism? These pain receptors are present in our internal organs, including the pancreas. Stimulation of TRPV1 sets of a pathway involving calcitonin gene-related peptide (CGRP), which blocks insulin release (see graphical abstract from their paper). Importantly, CGRP is also lacked in the sensory receptors of naked mole rats, famous for their longevity. In the most intriguing experiment of the paper, the researchers decided to block CGRP in normal mice, and saw a more youthful metabolism.

As usual, I remain skeptical about how translatable this is to humans. A cursory pubmedding doesn't show many studies looking at CGRP in aging humans, so whether the same pathway is intact remains to be seen. TRPV1 and CGRP inhibitors do exist, but I wouldn't go testing them in humans for anti-aging just yet. Still, it's an interesting mechanism, and shows how interconnected and complex the systems in our body potentially are.