So as we age, the heart undergoes specific, inevitable changes directly related to the aging process. It tends to get smaller and stiffer, and this can impact the heart's efficiency, potentially reducing our exercise capacity and elevating our risk for cardiac issues. But there can be exercise interventions, like consistent aerobic exercise with a high proportion of it being vigorous intensity, that can actually combat some of these effects. So there was a landmark study published from Ben Levine's group, and it was an intervention study that showed two years of vigorous exercise in 50-year-olds was able to reverse the aging of their hearts by as much as 20 years, effectively making their hearts look more like a 30-year-old, which in my opinion is simply astonishing. You're taking a 50-year-old heart and making it look like a 30-year-old heart. Now the exercise protocol used in this particular study gradually increased the exercise intensity and also frequency. So again, I mentioned it was a two-year intervention.

By the end of the first six months, participants were exercising about five to six hours a week, with a large portion of training being at the maximal steady-state intensity I referred to earlier in the podcast. It's sometimes called Zone 3. It is a type of vigorous-intensity exercise. They were also incorporating higher-intensity exercise. So they did the Norwegian 4×4 VO2 max training protocol I just referred to once a week. And I just think, like I said, it's simply astonishing that you take these 50-year-olds and, after two years of a more vigorous-intensity exercise training protocol, it essentially reversed the effects of aging in the heart. Okay, so let's shift gears yet again and talk a little bit about metabolic adaptations.

And again, this is where I think vigorous exercise really shines, particularly high-intensity interval training. It improves glucose control and insulin sensitivity more efficiently and more potently than even continuous moderate-intensity workouts. And I do think that, of course, both exercise-training protocols can enhance muscle adaptations and glucose regulation. HIIT really seems to do it quicker and, again, more robustly, whereas moderate-intensity exercise kind of demands longer sessions for comparable outcomes. So research has found that high-intensity interval training can enhance the muscle's ability to take up glucose and improve glucose transport capacity. During high-intensity interval training and vigorous exercise, there's a demand for rapid energy production.

And so the body relies on both aerobic, or oxygen-using, and anaerobic, or non-oxygen-using, metabolic pathways to generate this energy. The anaerobic pathway can lead to the production of lactate, especially when the intensity of exercise surpasses the point at which oxygen intake can keep up with energy demand. This is often referred to as the lactate threshold, as we talked about. For a long time, lactate was considered primarily a waste product contributing to muscle fatigue. And, you know, this has, of course, been completely reversed. Recent research has totally changed this understanding.

Lactate generated in muscle tissue is transported back into muscle and into mitochondria to be used as an energy source. When it starts to accumulate at higher levels, it also travels systemically and gets transported to other tissues like the heart, liver, and brain, where it's used for energy. It's also used as a signaling molecule. This is known as the lactate shuttle and was pioneered by Dr. George Brooks, who has really changed the field. He also happened to be my second podcast guest ever on this podcast. Anyway, I mentioned that lactate acts as a signaling molecule in those tissues as well. And you can think of a signaling molecule as a chemical messenger that sends a message to other cells.

One of those messages is the upregulation of glucose transport capacity. So during vigorous-intensity exercise and high-intensity interval training, when lactate production accumulates, it stimulates the expression and activity of glucose transporters on the muscle known as GLUT4. These are on the muscle-cell membrane. Lactate acts as a signaling molecule to increase glucose transporter activity on muscle cells. This then allows for more efficient uptake of glucose from the bloodstream into the muscle, even at rest. Consequently, insulin sensitivity is also improved and blood glucose levels are better regulated.

There have been several studies demonstrating that HIIT can improve glucose uptake, enhance insulin sensitivity, and decrease the risk of developing type 2 diabetes. This may be due to the intense metabolic stress created during HIIT, which leads to greater activation of glucose transporters and improved glucose clearance. So as I mentioned, both high-intensity interval training and continuous moderate-intensity exercise can be effective at improving glucose transport capacity in the muscles. HIIT promotes rapid increases in glucose transporters, allowing for efficient glucose uptake and utilization, whereas continuous moderate-intensity exercise, although it's less intense, still enhances glucose transport capacity. It improves the overall fitness of muscles as well.

So again, it just takes a longer duration of exercise to get there. With the lactate generated during high-intensity exercise, you're getting that immediate signal to increase GLUT4 transporters. And so it's a very rapid and robust adaptation. There are other metabolic adaptations. Just talking about mitochondria, mitochondria are very important and play a lot of roles in the body. But one of the most important is the production of energy in the form of ATP. This is obviously very important for muscles, but also hugely important for the brain, heart, liver, and pretty much every organ.

Athletes are very interested in mitochondrial health because they want their muscles to efficiently and effectively produce energy when they're training. But mitochondria are also very important in the context of aging. As we age, our mitochondria become less efficient at producing energy, and this poses a problem for physical activity, but also just for normal functioning of our organs. Now that problem of mitochondria not producing enough energy can actually be overcome by increasing the mitochondrial volume, or what's called mitochondrial biogenesis. And exercise, particularly vigorous exercise, is one of the best ways to do that. So one of the most powerful indicators of healthy mitochondria is the ability to generate new, healthy, young mitochondria called mitochondrial biogenesis.

Vigorous-intensity exercise, like the high-intensity interval training I mentioned, is one of the most powerful stimulators of mitochondrial biogenesis. This has to do with the metabolic stress induced by vigorous-intensity exercise. Lactate itself is a signaling molecule. When you're producing greater amounts of lactate, that activates one of the major pathways regulating mitochondrial biogenesis. It's called PGC-1 alpha. Again, lactate acts as a signal to produce more PGC-1 alpha. When we perform vigorous-intensity exercise such as HIIT, lactate is generated by the muscles and shuttled into mitochondria. Exercise increases the number of mitochondria per cell through mitochondrial biogenesis, allowing more lactate to be used as energy.