Intermittent challenges such as physical activity, fasting, heat, and cold exposure activate stress response pathways that help the body deal with stress and aging.

“Humans, we evolved to intermittently challenge ourselves. And before we had Instacart, where you could basically just get your food delivered to you, before the Industrial Revolution occurred, we were out hunting. And I say, we, not us but humans. We were out gathering. We were moving, and we had to be physically fit. You couldn't catch your prey if you were a sedentary slob, right? You were moving, and you had to pick your berries. You had to move. And so physical activity was a part of everyday life, and caloric restriction or intermittent fasting was also a part of it. This is another type of challenge. We didn't always have a prey that we caught, or maybe temperatures were such that there was nothing for us to gather, right? So food scarcity was something common as well as eating plants, so getting these compounds that I mentioned.”

“Well, and obviously you're doing things right. So cold and heat converge on some common pathways related to what you called intermittent challenge, which I love. I think, intermittent fasting, cold, heat, exercise, I mean, maybe even intermittent sleep deprivation.”

“These are all types of stress intermittent challenges that activate genetic pathways in our bodies. These are often referred to in science as stress response pathways because they respond to a little bit of stress. You know physical activity is strenuous. Fasting is a little bit stressful. Heat, cold, these things are all types of little intermittent challenges.”

“I mean, if you think about it, like you said, you know, in the case of heat, there's lots of examples of hormetic stressors. I mean, heat's one, there's fasting. There's a lot of xenobiotic, you know, compounds or xenohormetic compounds, like curcumin, these sort of things can...you know, they're slightly toxic in a small dose. And because of that small dose, I think dose is important, it activates, like you said, all these cellular stress response pathways that then help us deal with stress better. And guess what, aging is a stress.”

“But you know, it seems as though different types of stressors do have a more robust effect on certain types of stress response pathways.”

“If a person is exercising regularly and also doing some form of intermittent fasting and they're getting this activation of some of these stress response pathways and the beneficial effects, you know, metabolic switching, is there any need to also take in these plant phytochemicals that are also activating, you know, perhaps the same or different or both, you know, stress response pathways?”

“Throughout our human evolution, I guess, we have been exposed to these intermittent types of stress, whether it is periods of food scarcity because we didn't have Instacart and couldn't just order our food and have it delivered to us. We had to go out and hunt it and find it, gather, find berries and vegetables and things, and so food scarcity, there were periods of times when we were fasting. We were not getting food, and that activates a variety of stress response genes. A lot of times, these are called stress response genes such as autophagy genes, which are clearing out a lot of damaged stuff within a cell, inside of a cell, and they're very robustly activated by fasting, but they're also activated by other things like heat stress, so that's one form. Then there's the physical activity that also, I mean, again, we humans used to be a lot more physically active when that was our life, and we had to go and hunt and gather, and we worked in the field, agriculture, farming, I mean, just much more stuff that we were doing by moving around. That is another form of intermittent stress. Lots of stress response genes are activated.”