Why Some Stressors Make Us More Resilient

Christopher Bergland • Jan 04, 2022

Exercise induces "hormetic" adaptive responses that boost antioxidant defenses.

"Hormesis" describes the favorable adaptive response to something that would otherwise be a harmful stressor.
Exercise facilitates hormesis by increasing an enzyme called NOX4 in skeletal muscles; NOX4 boosts antioxidant defenses.
Exercise-induced reactive oxygen species (ROS) may drive hormetic adaptive responses that prevent oxidative damage.

When Kelly Clarkson belts out her interpretation of Nietzsche's famous aphorism in her 2012 smash hit, "Stronger (What Doesn't Kill You)," she's probably not thinking about the hormetic effect a grueling workout has on kickstarting adaptive responses that increase resilience via the expression of an enzyme called NOX4.

What Is Hormesis?

Hormesis is a dose-response phenomenon in which a potentially harmful substance can benefit a living organism.

New research in mice (Xirouchaki et al., 2021) suggests that exercise triggers a favorable (hormetic) adaptive response to stressors that would otherwise be harmful. Because of hormesis, when it comes to exercise, in many ways, "what doesn't kill you" does, in fact, "make you stronger."

Accumulating evidence suggests that the induction of mitochondrial biogenesis, which enhances respiratory capacity and boosts endurance, is a vital hormetic response to exercise. The latest findings on how exercise-induced NOX4 is required for hormetic adaptive responses were published on December 15 in the peer-reviewed journal Science Advances.

"Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise," the authors explain in their paper's abstract. "Here, we demonstrate that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance."

Hormesis in Action: NOX4 Transforms Potentially Harmful ROS Into Something Beneficial

Theoretically, without skeletal muscle NOX4, exercise could be toxic. In mice treated with a substance that blocked NOX4, the researchers found that aerobic exercise increased oxidative stress. According to the researchers, this demonstrates that NOX4 is "essential for promoting antioxidant defense and mitochondrial biogenesis, preventing mitochondrial oxidative stress, and maintaining insulin sensitivity."

Xirouchaki et al. also report that skeletal muscle NOX4 tends to decrease with age and obesity; these factors can lead to the development of insulin resistance. "Our findings demonstrate that skeletal muscle NOX4 is of fundamental importance in exercise-induced hormetic responses that promote muscle function and metabolic health," the authors explain.

When NOX4 is depleted, aging and obesity can increase "harmful" mitochondrial ROS production that causes oxidative stress. However, exercise-induced ROS is hormetic; it triggers a "helpful" adaptive response that prevents oxidative damage. NOX4 is essential for this antioxidant defense response.

Exercise-Induced Mitochondrial ROS Boosts Antioxidant Defenses. But How Much Exercise Is Too Much or Not Enough?

"Triggering the activation of the adaptive mechanisms orchestrated by NOX4 with drugs might ameliorate key aspects of aging, including the development of insulin resistance and type 2 diabetes," senior author Tony Tiganis of the Department of Biochemistry and Molecular Biology at Australia's Monash University said in a news release.

Human studies are needed to see if the adaptive mechanisms triggered by exercise have the same effect on NOX4 production in people as Tiganis and colleagues observed in mice. Future research should also identify the ideal "dose" (duration/intensity/frequency) of cardio and/or strength training workouts needed to activate an optimal hormetic response.

In terms of hormesis and optimizing the exercise-induced generation of ROS by skeletal muscle NOX4, there's probably a sweet spot between doing too much or too little physical activity throughout the week. But we need more research to clearly define this Goldilocks zone.

Until we know the optimal dose-response for hormesis, doing 150–300 minutes of moderate-intensity cardio per week or 75–150 minutes of vigorous-intensity aerobic exercise plus two strength-building workouts per week has been shown to have innumerable benefits. (See "New Physical Activity Guidelines Based on Decade of Research.")

This article originally posted at Psychology Today.

Christopher Bergland is a retired ultra-endurance athlete turned science writer, public health advocate, and promoter of cerebellum ("little brain") optimization.

< Older Post Newer Post >

Orange County Psychiatric Associates, in Mission Viejo, works with adolescents, and adults to enable them to live their lives to their fullest. Orange Coast Psychiatric Associates tailors treatments based on the understanding that both body and mind must be treated in order to promote better mental and physical health. Let us help you improve your quality of life with specialized care for you.

BOOK APPOINTMENT

Study: Adult ADHD and Depression, Anxiety Strongly Linked

By Melanie Wolkoff Wachsman • 16 Feb, 2023

ADHD traits are linked to more severe anxiety and depression symptoms in adults than are traits of autism spectrum disorder, according to a new U.K. study that underscores the importance of screening of ADHD comorbidities.

Psychiatric disorders linked with higher risk for heart disease, diabetes death

By Brian P. Dunleavy • 25 Mar, 2022

(UPI) -- People with mental health disorders are up to twice as likely to die earlier from chronic conditions such as heart disease and diabetes than those without them, a study published Thursday by PLOS Medicine found. Among people with psychiatric disorders such as anxiety, depression, bipolar disorder, substance use disorder and schizophrenia, 21% died within five years of being diagnosed with heart disease, diabetes or breathing problems, such as chronic obstructive pulmonary disease, the data showed. Of those without diagnosed mental health disorders, 9% died within five years of learning they had one of these chronic conditions, the researchers said. Compared with unaffected siblings, people with mental health disorders were about seven times more likely to die within five years of being diagnosed with a chronic physical health condition and nearly nine times more likely to die by suicide within that time frame, according to the researchers. Of all the participants in the study, 7% died of any cause within five years of being diagnosed with a chronic condition and 0.3% died by suicide, they said. "We used electronic health records to investigate over 1 million patients diagnosed with chronic lung diseases, cardiovascular diseases and diabetes," study co-author Dr. Seena Fazel said in a press release.

Is Social Media Increasing Eating Disorders In Teens?

By Peter Suciu • 18 Mar, 2022

Teens who spend more time on social media could be far more likely to developing eating disorders. According to new research teens who spend just 30 minutes a day could have increased feelings of anxiety, depression, loneliness and notably poor self-image, the latter of which could lead to unhealthy eating behaviors. Researchers in Australia, lead by Dr. Simon M. Wilksch of Flinders University , looked at the effect that social media had on body image, and the results of the study were published in the International Journal of Eating Disorders. It found that eating disorders "were reported by 51.7% of girls and 45.0% of boys, with strict exercise and meal skipping the most common. A total of 75.4% of girls and 69.9% of boys had at least one SM (social media) account where Instagram was the most common, used by 68.1% of girls and 61.7% of boys." The research found that it wasn't one particular form of social media that could be leading to the eating disorders either. Girls in the study, who may be prone to eating disorders, were more likely to use SnapChat and Tumblr, while boys also used Snapchat, but were more active on Facebook and Instagram.

Psychotherapy for Individuals, Children and Couples.