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Sunday, 28 February 2021

Hormesis: Meet The Stress That Makes You Physically & Mentally Stronger

You know the old saying, "What doesn't kill you makes you stronger"? Science has revealed that (at least in some situations) it's surprisingly accurate—even down to the cellular level. 

We're talking about hormesis, 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.

But how is putting your body through "hormetic stress" good when you've been told for years that stress is straight-up toxic? It's all about the specific stressor and the dose. (Spoiler: Intermittent fasting is a hormetic stressor.) Let's dive into the science (it's really cool, we promise!); plus ways to strategically stress yourself out.



What is hormesis? The health-enhancing stress you need in your life.
There's no question that chronic stress caused by things like an unsustainable workload, poor relationships, lack of sleep, or financial hardships can wreak havoc on your health. 

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.

But how does it actually work?
A range of very different habits and substances fall under the umbrella of "hormetic stressors," but they activate similar processes. "Some of the same systems are turned on whether you're taking a cold plunge or eating broccoli sprouts," says Rountree. Pretty cool, but how does it work? Surprisingly, oxidative stress seems to be one of the big underlying mechanisms. 

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 pathways, 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). 

6 ways to strategically stress your body and reap the health benefits.
Don't worry, you don't have to go on a multiday fast or start doing cryotherapy. There are a bunch of small, sustainable habit changes that can help you reap the benefits of hormesis:

1. Do workouts that challenge you.
High-intensity interval training (HIIT)—characterized by intermittent bursts of all-out effort for about 30 seconds followed by 15 seconds of rest—is one of the most efficient ways to experience hormesis. During these intense bursts, your muscles are briefly starved for oxygen (hypoxia), which stimulates the production of mitochondria. You're also activating fast-twitch muscles, which may be beneficial for longevity. Any exercise that challenges you, whether it's an intense spin class or a boxing workout, is also a good choice, says Macciochi. Keep yourself balanced by alternating them with slower, restorative workouts like yoga.

2. Incorporate breathwork into your routine.
While we need more research to flesh out the perks, holding your breath for as long as is comfortable from time to time may be a good way to experience intermittent hypoxia and improve lung capacity, says Rountree. You can do this when you're sitting at your desk or lying in bed. For a more subtle approach, you can try box breathing, which involves inhaling through your nose for four seconds, holding it for four seconds, exhaling through your mouth for four seconds, then holding the exhalation for another four seconds. 

3. Get out of your temperature comfort zone. 
Saunas, hot baths, working out on a warm day, or even taking a hot yoga class are all ways to reap the benefits of heat. Sauna use, specifically, has been associated with reduced all-cause mortality risk; and periodic heat exposure, in general, can boost the expression of "heat shock" proteins in the body, which may help strengthen the immune system and promote longevity. 

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.

4. Eat lots of colorful plant foods.
Even phytonutrient-rich plant foods can activate your healthy hormetic stress response—the term for this is xenohormesis. The glucosinolates in broccoli sprouts, for example, are thought to activate beneficial phase II detoxification enzymes by way of the Nrf-2 pathway, says Rountree. Other xenohormetic nutrients include curcumin from turmeric, resveratrol from berries and wine, allicin from garlic, quercetin from a variety of fruits and vegetables, and even green tea, says Rountree. Typically, plants exposed to more stress in their environment will produce the highest levels of these beneficial compounds. A good general rule: Look for bright colors. 

5. Experiment with intermittent fasting.
Intermittent fasting puts your body into a perceived state of stress due to temporary nutrient deprivation. Fasting inhibits a cellular process called mTOR (mechanistic target of rapamycin), thus triggering a cellular cleanup process known as autophagy, which may contribute to better cellular health and longevity. The type of fasting you choose depends on a variety of factors, but you don't necessarily have to do anything too intense to reap the benefits. Consider confining your eating to an eight- or 10-hour window, or try a fasting-mimicking diet. 

6. Engage in mentally stimulating and challenging activities. 
Learning new skills, engaging in challenging mental work, and having a lot on your plate can also constitute hormetic stress. We often equate psychological or mental stress with being bad, but according to Rountree, these challenges can stimulate some of the same cellular pathways mentioned above—and even generate brain-derived neurotrophic factor (BDNF), which promotes neuroplasticity. There's one big caveat, though—in order for you to reap the benefits from psychological stress, you need to feel like the stressor is manageable and that you're in control. If you feel helpless, the stressor becomes toxic. 

Beware, you can have too much of a good stressor.
While you may be psyched to incorporate all of these hormetic stressors into your life, know that it's possible to overdo it. Certain things like eating a colorful, nutrient-rich diet are always a great idea. But before you engage in some of these more intense activities, such as intermittent fasting or HIIT, assess your current stress levels. 

"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.

Bottom line.
Hormesis is proof that healthy stress does exist. Intermittent doses of "hormetic stressors" like cold exposure, intermittent fasting, and HIIT exercise can stimulate powerful cellular pathways that support overall health. These practices may help you become more resilient to life's physical and mental challenges—which is more important than ever.

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