In an engine running at full throttle, the pistons wear out over time. In a young body, that engine is the IGF-1 signaling pathway, which drives cells to grow and divide. But in old age, the same mechanism no longer repairs; it accelerates wear. It's like a gas pedal that should be eased off in old age. Scientists have long suspected that gently slowing this pathway in adults could extend healthy life. The problem was finding a safe brake that could simply be added to food.
The experiment involved 150 mice, half male and half female. Some received regular food, others food with PPP, and others with NVP-ADW742. They were monitored almost until the end of life, up to 151 weeks. The results were encouraging. In mice receiving the drugs, memory remained at youthful levels, while in controls it declined noticeably. In males, blood pressure dropped and glucose tolerance improved. In females, fur barely grayed: only 0.6–0.9% gray hairs versus 2.9% in controls. And the frailty index, a measure of how decrepit a mouse has become, fell by a factor of three.
However, both substances turned out to be poor drug candidates. PPP is unstable and caused stomach bleeding as a side effect. NVP-ADW742 is poorly absorbed, rapidly cleared, and may disrupt heart rhythm. So they cannot be used in humans right now. But the principle itself, slowing IGF1R in late life, has been confirmed. The remaining task is to create a cleaner, safer brake.
So what did this work achieve? Previously it was unclear whether IGF1R could be safely suppressed in adult mammals with simple molecules taken orally, and whether it would have an effect. Now it has been shown: yes, it can, and the effect is there. This was achieved by comparing mice receiving the drugs with food to a control group over almost their entire lives. This will be useful for developing new, safer IGF1R inhibitors as potential geroprotectors for humans. The gas pedal in old age can be eased off if you find the right brake.
In female mice receiving IGF1R inhibitors, the coat remained black and glossy until death, whereas control animals turned gray. This brings to mind the folk observation that stress and growth hormones accelerate graying.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.