 In the year 2000, a new human hormone was discovered. It was the 21st documented fibroblast growth factor, so they called it FGF21. Since this discovery, FGF21 has emerged as a key agent for promotion of metabolic and artery health, leanness, and longevity. Injected into fat monkeys, and they lose body weight without reducing food intake. They're not just a little, a 27% drop in body fat, eating the same amount. In mice, it increases their lifespan 30 to 40% comparable to life-long caloric restriction, but again was achieved without decreasing food intake. The researchers conclude that FGF21 could potentially be used as a hormone therapy to extend lifespan in mammals, which has gotten big pharma salivating, increasing the question, can aging be drugged? And that's not all it can do, the idea that one drug can treat obesity, diabetes, dyslipidemia like high cholesterol, and hypertension all at once might have seemed impossible a few years ago, but is now a tantalizing and exciting prospect. The reason you can't just give people straight FGF21 is that it gets rapidly broken down in the body, so you'd have to get injections like every hour or two around the clock. So drug companies try to patent a variety of longer-acting FGF21 look-alikes, and indeed give people little PF050 to 31023, and they can lose about 10 pounds in 25 days, along with dramatic drops in triglycerides and cholesterol. But then the side effects of these newfangled drugs started cropping up. Okay, so hey, what about this? We package the FGF21 gene into a virus, and then inject the virus and have it like stitch extra FGF21 genes into our DNA, or you can just lace on your running shoes. Exercise boosts FGF21 levels, which may in fact be one of the reasons exercise is so good for us. Which works better, though? Aerobic exercise, eight weeks of running, training, or resistance exercise, eight weeks of weights? The answer is both. But the resistance exercise edged out the running, a 42% increase in FGF21 versus a 25% increase in the aerobic exercise group. Okay, but what can we do with food? Yeah, you could try engineering and injecting it, but wouldn't it be easier to just stimulate our own endogenous natural production through diet? One way is through no diet at all. You may have noticed it's been dubbed the starvation hormone. It's because fasting induces FGF21, but not just a day or two. Physiologically, FGF21 expression is markedly increased in response to fasting starvation, but unlike mice, which show an increase after just six hours of fasting, humans don't get a notable surge in FGF21 until after a week. Fasting can quadruple FGF21, but it takes 10 days of fasting, which is the very poster child of an unsustainable eating pattern. So, how can you get the benefits without the starvation? Might a ketogenic diet be able to mimic the fast? Nope, keto diets don't work. In fact, keep it up for a few months and you can actually get a significant decline in levels. High-fat diets may even interfere with the boost you get from exercise, seen here in a study of high-intensity interval training. What kind of diet does work, then? We'll find out next.