Metformin and Caloric Restriction The only intervention that is known to consistently extend life span across many different species is caloric restriction. Animals seem to be widely adapted to stabilize their populations by suppressing death from aging under conditions of starvation (and raising the internally-programmed death rate when there is plenty of food). How does the individual metabolism detect when it is starving? The signal comes mainly from the insulin metabolism. The body responds to chronically elevated insulin by decreasing sensitivity to insulin, and raising insulin levels yet further in a positive feedback loop that cascades toward death. Metformin interrupts this cycle in a manner similar to lowered food intake. Since most people don’t tolerate chronic hunger very well, a drug that offers the benefits of a lean diet without having to cut calories would be highly prized. Such a drug is called a caloric restriction mimetic, and there is some reason to believe that iswhat metformin does. (Many people taking metformin experience actual weight loss as well.) The health benefits of metformin for diabetics are striking, and are not shared by other drugs that treat only the diabetes. Metformin . But cancer is already elevated in diabetics. If the reduction in cancer had been to values below the rates in non-diabetics, then metformin for non-diabetics would seem to be a slam dunk. But in reality this sizable benefit brings cancer rates down , but not further. So the benefits for non-diabetics remain speculative. Life extension in rats and mice Over the years, there have been many studies of metformin’s effects on mice and rats. Most show some life extension, and the best result increased life span by 38%. Metformin seems to work better for mice than rats, and better for females than males. Here is a table () summarizing results in rodents. Strain Sex Treatment No. of animals Life span, days References Mean Last 10% of survivors Maximum Mouse C3H/Sn
