We’re talking about hormesis1, or the idea that short, intermittent bursts of certain stressors (“hormetic stressors”) can actually trigger a cascade of cellular processes that enhance overall health, slow aging, and make you more resilient to future stress (both physical and mental). It’s weird and fascinating stuff, and one of the hottest areas of longevity research right now. Hormetic stressors, on the other hand, are controlled, acute stressors that trigger healthy adaptive responses. Hormesis has a dose-response relationship and represents how “high doses of certain substances or exposures can have a toxic effect, while low doses can be beneficial,” says integrative physician Robert Rountree, M.D. “It’s the periodic nature of the stressor that defines hormesis—short-lived doses of stress activate positive response patterns.” What does this look like in real life? Researchers have found that hormesis is a common thread underlying many of the health benefits associated with intermittent fasting, cold exposure, heat exposure, high-intensity interval training (HIIT), intermittent hypoxia, and even certain phytonutrients found in plant food, like the glucosinolates in cruciferous vegetables. High or prolonged doses of any of these behaviors or substances aren’t sustainable or healthy (spend too much time in cold water, and you’re gonna get hypothermia). But in short bursts, the little bit of irritation that these stressors cause is just enough to knock you out of comfortable homeostasis and activate a variety of cellular mechanisms and signaling pathways that promote stress resilience, repair cellular damage (via processes like autophagy), repair DNA, combat oxidative stress, produce new mitochondria, reduce inflammation, support elimination of toxins, improve blood sugar regulation, reduce risk of cancer, and more, explains Rountree. In fact, some experts believe that if you don’t expose yourself to enough hormetic stress, it’s hard to achieve optimal health and well-being. In a 2020 research review, Elissa Epel, Ph.D., director of the University of California–San Francisco Aging, Metabolism and Emotion Center, writes that “biologically, the lack of acute stressors prevents the intermittent episodes of cellular ‘housecleaning’ activities that slow aging.” There’s also increasing evidence that the stress resilience we obtain from one hormetic stressor may help the body adapt to other stressors—even to psychological stressors like depression and anxiety—which is called “cross-adaptation,” according to Jenna Macciochi, Ph.D., author of Immunity: The Science of Staying Well. Most of the hormetic stressors mentioned above—from HIIT exercise to certain phytonutrients—actually generate low levels of free radicals in the body. This may sound bad, but here’s why it’s not: Our mitochondria, which are responsible for producing the energy our cells require to function, actually generate more copies of themselves in the presence of some free radicals, says Rountree. As you get older, you tend to lose mitochondria (in fact, it’s a hallmark of aging), which can leave you tired and without the energy to optimally fuel cellular processes. So, by stimulating mitochondrial biogenesis, you can enhance both short- and long-term health. The bursts of oxidative stress generated by hormesis also influence a variety of cellular signaling pathways1, including one involving the transcription factor Nrf-2. (Transcription factors are proteins that bind to DNA to activate genes.) The presence of free radicals prevents Nrf-2 proteins from breaking down as quickly. This means more Nrf-2 can travel into the nucleus of cells, where it binds to DNA and triggers the production of powerful antioxidant enzymes like glutathione (the body’s “master antioxidant”) and phase II detoxification enzymes. These enzymes, in turn, make the body more efficient at neutralizing toxins and high levels of oxidative stress. So, oddly enough, by triggering a little oxidative stress now, hormetic stressors can help you neutralize more oxidative stress later. Nrf-2 is just one example of how hormesis boosts health. Other hormetic cellular pathways include AMPK, FOXO3, SIRT1, and mTOR—many of which are activated simultaneously and have overlapping effects (some of which are described here). Ice baths, cold showers, or even spending time outside when it’s cold can be beneficial, too. Regular cold exposure has been shown to boost levels of certain immune cells, including cytotoxic T-cells, which play a role in killing virally infected cells and cancer cells, and it can significantly boost the life span of certain animals. Both heat and cold exposure have also been associated with mitochondrial biogenesis. “We all have a certain capacity for stress, and some people have a smaller cup than others,” says Macciochi. “When your stress cup is already overflowing, it may not be appropriate to then enter more acutely stressful hormetic situations. Hormesis should be a thing we do to future-proof us against stressful situations and be done when we feel relaxed, not when our stress cup is already full.” Consider taking it easy the week before your period, too. This is when your estrogen levels experience a steep drop, which leads to cortisol sensitivity (our stress hormone)—so your body is much more susceptible to the effects of additional stressors.
