But I think one of the most convincing studies that I've seen for vigorous-intensity exercise has to do with structural changes in the aging heart. So as we age, our heart undergoes structural changes, it gets smaller in size, and it gets stiffer. And this translates to functional deficiencies like exercise capacity goes down, but also it increases the risk for cardiovascular disease, a lot of different— changes start to happen in the cardiovascular system when that occurs. There was a study done at UT Southwestern in Dallas by Ben Levine's group where they took 50-year-olds that were disease-free, but they were sedentary. They didn't have type 2 diabetes or cardiovascular disease, but they weren't physically active. They put them on two different exercise protocols.

One was the control group, which was more like a stretching, a little bit of a bodyweight training. It wasn't high-intensity, they weren't really getting their heart rate up, a little more like a yoga-ish type of workout. And the other group did that, but they also had a high-intensity, like vigorous exercise workout program. And this was a 2-year intervention study, and so the first 6 months was like a progressive building up their endurance, and once they got to the 6-month mark, most of these people were doing about 4 to 5 hours a week of training, and a good portion of that time was spent in what's called maximal, your maximal state, exercise state, where they were doing like 20 to 30 minutes a day of maximal intensity exercise, not maximal intensity, but steady state.

So they were able to basically maintain the maximal amount of intensity they could for 20 or 30 minutes. So it was vigorous. They were going 75%, 80% max heart rate. They also did the Norwegian 4x4 protocol once a week. And after those 2 years, the structural changes in their heart reverted back almost 20 years. So their hearts got like more malleable and they got larger, and it was like looking at a 30-year-old heart, and these were 50-year-olds. To me, it was just so astounding that you could get structural changes in the heart, essentially reversing the aging heart by just about 20 years from doing this vigorous-intensity exercise protocol in 50-year-olds that were sedentary. There's also drug-sized blood pressure improvements with vigorous-intensity exercise.

There's been a variety of randomized controlled trials and meta-analyses of these trials that have found people that work out and do more vigorous-intensity exercise 3 to 4 days a week, about 20 to 60 minutes of vigorous-intensity exercise, can improve their blood pressure similar to medications like antihypertensive medications. High blood pressure is not just a risk factor for cardiovascular disease. It's now been established that it's one of the most important early risk factors for dementia and Alzheimer's disease. The fact that you can comparably get these improvements in blood pressure like you would get with a pharmaceutical drug is also, I think, extremely encouraging. I want to shift gears just for a minute and get into some of the brain benefits.

I think probably one of the most convincing reasons to get your heart rate up high, when I say high, I mean 75-80% max heart rate, to do that is from brain benefits. That largely has to do with something called lactate, which probably many of you are familiar with. When you force your muscles to work so hard that you can't get oxygen to them fast enough to make energy, they have to adapt. They use glucose as energy without the mitochondria, which is generally how you're making energy. As a byproduct of that, you're churning out lactate, which was thought to be this metabolic poison byproduct. It turns out it's much more than that.

And so lactate gets into circulation and it's taken up by other tissues, including the muscle, the brain, the heart, liver, and it's used as energy in those tissues. So it's a very energetically favorable source of energy. It's actually easier to make energy from lactate than from glucose. So it takes less energy to make energy from lactate than glucose. But also, it acts as a signaling molecule. It's a way for your muscles to communicate with other parts of your body. Because, you know, when you're exercising, it is a stress on the body. And so, adaptations happen, right? When you're working your muscles hard, you can, you know, increase muscle hypertrophy.

These adaptations happen, cardiovascular improvements, you're getting increases in stroke volume, cardiorespiratory fitness improvements. Well, the brain also works really hard during exercise. And so lactate is communicating with the brain, and there's many benefits to having lactate go into the brain. And one of those is that it signals to the brain to make something called brain-derived neurotrophic factor, or BDNF. And what this is is a growth factor that is involved in increasing new neurons inside the hippocampus and other regions in the brain, but mostly the hippocampus, which is important for learning and memory. There's been intervention studies showing that aerobic exercise in older adults who do it for 2 years increases their hippocampal volume by like 2%.

It increases neurogenesis, but it also is important for neuroplasticity. This is the way your brain adapts and is able to adapt to the changing environment and still function. It plays a big role in depression. People that are depressed have a very low level of neuroplasticity, and so they have a hard time adapting to the changing environment, which causes depressive symptoms. So brain-derived neurotrophic factor is like amazing for your brain. You want more of it, and high-intensity exercise is the way to get more of it. Lactate also signals to the brain to make neurotransmitters like norepinephrine and serotonin. These studies have been done in humans.

Lactate, again, made from muscles when you're forcing your muscles to work hard, when you're going high-intensity, crosses over the blood-brain barrier, and your brain is working hard during exercise, and so lactate is fueling that, your brain function during exercise, but it's also increasing things like norepinephrine, which is involved in focus and attention, serotonin, and there have been studies showing that even 10 minutes of a high-intensity interval training workout can improve cognition, improve mood. I mean, it's just really easy to get those improvements in just a short amount of time by like, you know, just getting after it pretty hard. Some of the protocols that have shown improvements in maximizing BDNF really are intensity and duration dependent.

So the harder you go, 80% max heart rate for 30 to 40 minutes is one of the most robust ways. There's also another really good protocol. So this would be 6 minutes of high-intensity interval training where you do about 40-second all-out intervals separated by some recovery periods that also has been shown to pretty robustly increase brain-derived neurotrophic factor as well. I just wanted to spend just a second talking about some of the anti-metastatic effects of vigorous-intensity exercise. Most of us here know that exercise is one of the best things you can do to prevent cancer, but also as an adjunct cancer treatment. Many different ways that's occurring, but one interesting way that most people don't know about is through the shearing forces of your blood just blood flow.

So just getting that blood flow to go faster by exercising, by getting that exercise, kills what are called circulating tumor cells. These are tumor cells that have escaped a primary site of the tumor, get into circulation, and they go and, you know, try to travel to other tissues and take camp there and, you know, metastasize. Well, circulating tumor cells are very sensitive to the mechanical forces, the shearing forces of blood flow. And they can't handle the stress like our normal cells can, and they die. And so I just think that's a really interesting way to think about it because it's like, oh yeah, I need to get my blood flow up. I need to get my heart rate going and my blood flow up, and that is something that has an anti-metastatic effect.