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In this editorial, Leslie Kenny, Founder and CEO of Oxford Healthspan, explains the role of autophagy and stress and how to ensure you are supporting your body’s ability to respond.

The house is a mess, dinner burnt, the teenagers stroppy, the slides for tomorrow’s work presentation unfinished, and we can’t get out of the house because it’s pouring rain. Sound familiar? The details may be different. However, I’m sure we’ve all had moments like this—when it’s all a bit too much. Whether you call it stress, the definition perfectly encapsulates this moment: where the demands outweigh the resources. This is where autophagy comes in and why it’s so very important to ensure our bodies are able to clean up the damage we suffer from stress.

The Pathology of Stress 

I’m sure that it’s no surprise that stress isn’t restricted to your thinking—we have physiological responses to stress. It deregulates the normal functioning of the body in a variety of ‘fun’ ways: The hypothalamic-pituitary-adrenal axis produces stress hormones that block immune responses, lowering the counts of T-cells, B-cells, and NK-cells. 

Inflammatory responses also become uncontrolled with the overproduction of cytokines, increasing the body’s susceptibility to viral infection. This comes as no surprise, of course. When we have periods of high stress, our (immune) defenses are down, and we’re more likely to become sick.

The fun continues inside the cell with functional and structural changes to the mitochondria, the energy centers of the cell; these changes can extend to DNA and gene expression thereby increasing the susceptibility of disease. It’s not hard as a modern human (not a scientist) to make the connection between chronic stress and feeling badly; now, we know why.

What about our behavioral responses to stress?

Humans have a variety of techniques to “handle” our stress and most of them are bad: Researchers see an increase in smoking, drinking alcohol, and eating in response to stress. Women, in particular, are prone to overeating; a study of middle-aged American women, for example, found that middle-aged women who reported higher stress were more likely to use food as a coping mechanism.

Researchers also see a decrease in adaptive responses like sleep and exercise among stressed individuals. My particular stress response cocktail is a combination of not getting enough sleep, skipping my workout in favor of more work, and raiding the cabinet for dark chocolate; it doesn’t go well.

Oxidative Stress

Our physiological response to stress, and many of the mechanisms for coping with it, increase another type of stress, oxidative stress. We would be remiss not to mention it, as it is the most relevant type of stress at the cellular level.

More precisely, oxidative stress is caused by an imbalance of highly reactive oxidizing compounds. Reactive oxygen species (ROS), for example, are one of the main flavors of oxidizing molecules and about 1 billion of them are produced intracellularly (mostly in the mitochondria) each day. Oxidizing molecules have the ability to take electrons from other molecules in close contact, which can lead to destabilization and damage.

But, at low concentrations, they do have roles to play: for example, in cell signaling, synthesis of some cellular structures, and helping to fight pathogens. The key to keeping the oxidizing compounds at the beneficial level, comes down to the cell’s ability to clear or deal with them.


Oxidative stress is minimized by preventing the accumulation of damaged cytoplasmic debris or cell trash.

Autophagy, a recycling mechanism that “cleans up” the obsolete, damaged, or toxic cell contents – via the cell’s very own Marie Kondos – plays a prominent role. Rates of autophagy are highly regulated to sense intracellular stress (and to increase in response), but regulation of autophagy is impacted by a variety of factors.

For example, we know that rates of autophagy decrease with age (we don’t want that when the deadlines are stacked). We also know that there are things we can do or lifestyle changes that we can make to increase our rates of autophagy.

Ways to Induce Autophagy

  1. Deep sleep

By preventing the buildup of waste in brain cells, sleep promotes autophagy by poorly understood mechanisms. Sleep deprivation leads to defective oxidative stress management, the accumulation of cellular waste, and mitochondrial dysfunction, all of which lead to less energy and compromised cells. Try to catch some Zs!

1. High intensity exercise

While the pathways are not fully understood, the high intensity – particularly intensive, prolonged cardio has been shown to have a global (full body) autophagic response. Shorter bouts of exercise have been shown to induce autophagy in skeletal muscle. Break out the running shoes!

autophagy and stress2. Calorie restriction

Calorie restriction – of which fasting, temporary or intermittent, is a type – is a long-term reduction in calorie intake (eating a bit less for a long while) without malnutrition. Rates of autophagy increase in response to perceived “starvation.”

3. Calorie restriction mimetics (CRM)

CRMs, or foods and supplements that mimic or induce similar effects to calorie restriction and activate autophagy. For example, the CRM spermidine can be found in many foods such as aged cheeses and wheatgerm and in supplement form; we recommend, however, reading your labels as not all supplements are created equal.

Bottom Line on Handling Stress

It seems that all manner of evil – including the negative effects of stress – can be at least partially managed with good sleep, good eats, and getting the heart rate up through exercise.

Every time I explore what the research says about stress, I’m struck by the beautiful simplicity of Japanese doctors prescribing a walk in the woods to their overwhelmed and anxious patients.

Next time my daughter takes her diaper off in protest, I think we’ll grab a spermidine snack and go for a walk in the park…with umbrellas.

Leslie Kenny is the Founder and CEO of Oxford Healthspan. Her full biography is listed below.


Main photo credit

Autophagy and stressPhoto by Lacie Slezak on Unsplash

Leslie Kenny

Leslie Kenny

Oxford Healthspan was founded by Leslie Kenny, a Southern Californian entrepreneur and graduate of both Berkeley and Harvard, whose life was turned upside down when she was diagnosed with lupus and rheumatoid arthritis in her 30s. When her doctors told her lupus had a life expectancy of five years and that RA could only be managed, not cured, she set out to optimize her health as best she could with safe, natural solutions. She went back to school at the Institute for Integrative Nutrition in NYC, became a Bulletproof coach under health pioneer Dave Asprey, and took on health coaching clients worldwide. At the same time, she began helping life science academics at European universities, including Oxford (where she lives), to raise money for their discoveries. At a meeting with one such scientist, she learned about a natural compound called spermidine, abundant in nattō, a traditional Japanese dish that she had grown up with. Spermidine was showing great promise supporting health as we age. The science was compelling – one scientist even called it “an anti-aging vitamin” in a published scientific journal – and it was safe. Still, because it was natural, food-derived, and not a drug that would bring in more money, no one was interested in promoting it. Leslie immediately wanted her octogenarian mother back home in California to take it – especially since nattō is very hard to come by (it's pretty smelly, for one thing!) Unfortunately, spermidine wasn't available in the US (or really even known there). Spotting this unmet need, she decided to bring it to the US herself. Today, at age 56, Leslie is living proof that we can get better with age, so long as we take responsibility for our health and meet our doctors halfway. Spermidine is part of her anti-aging arsenal, and she hopes it will become part of yours too.


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