I know we’ve all heard of the old saying “What doesn’t kill you makes you stronger” but have you ever wondered if science could open our eyes to what exactly this means? I’ve wondered this, and it led me to this week’s Brain Fact Friday where we will explore hormesis or the idea that “short, intermittent bursts of 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).”[i]

On this episode you will learn:

✔︎ How our cells respond to short, intermittent periods of stress.

✔︎ A look into 2 pathways that are important for longevity (The Sirtuin and mTOR).

✔︎ 4 Ways to boost our health, using hormesis or stress, making us physically and mentally stronger.

For those new, or returning guests, welcome back! I'm Andrea Samadi, author, and educator from Toronto, Canada, now in Arizona, and like many of you who tune in, have been fascinated with learning, understanding, and applying the most current brain research to improve productivity in our schools, our sports, and workplace environments. The purpose of this podcast is to take the mystery out of this new discipline that backs our learning with simple neuroscience to make it applicable for us all to use right away, for immediate results.

I had no idea while initially researching for this episode that neuroscientist and tenured professor in the Department of Neurobiology at the Stanford University School of Medicine, Dr. Andrew Huberman, would be hosting Dr. David Sinclair[ii] (a Professor in the Department of Genetics from Harvard Medical School) on the Huberman Lab Podcast this week, and covering this very topic on “The Biology of Slowing and Reversing Aging”[iii] where the idea of hormesis was discussed throughout. I do recommend this episode for those who want to take a deeper dive into the science of anti-aging, longevity and the fascinating work that Dr. David Sinclair is doing in this field, in addition to Dr. Peter Attia’s Podcast, The Drive, on “Dr. Sinclair, Ph.D. Slowing Aging, sirtuins, NAD, and the epigenetics of aging.”[iv]

If you are listening to this, and thinking “What? She’s lost me! What is she even talking about? Slowing down the ageing process? What is NAD and what are sirtuins?”  Just remember to keep an open mind--this podcast focuses on looking for the research from the most reputable place (Pubmed.gov), learn what the experts in the field have to say about what they are discovering, and then we break down the research in smaller pieces,  so that we can all make it applicable in our daily life, whether we’ve taken a neuroscience course, or not. What I’ve learned from studying closely with neuroscience researcher Mark Robert Waldman the past few years, is that we must be open to what the research says and keep our egos (and judgements) out of whatever it is we want to prove. I’m working hard on an abstract that supports the importance of educational neuroscience as a new discipline in our schools, versus the old model of learning, and although there is research that supports my hypothesis, it’s still a new field, and I must remember what Dr. Sinclair tells his students, that “most things we thought were true are not…or will change over time.”[v] I’m now on my third revision of this abstract, because it’s not easy to step away from what we want to believe, and leave it up in the air, because we might be wrong about everything, when it comes to looking at life through the lens of a scientist.

Just keep an open mind, especially when you hear that Dr. Sinclair, now at the forefront of anti-aging research, after all the criticism he’s received over the years, is in the late stages of clinical trials of working on something that mimics exercise in a pill to speed up metabolism. The next few years are going to really blow our minds with what is possible, and I hope that we can all embrace new ideas, with open minds and make the needed change with what we learn from the research, whether it’s in the classroom like I’d like to see with new models of learning backed by neuroscience, or in the modern workplace.

Moving into Season 7 of this podcast in the New Year, with a focus on Brain-Health and Well-Being, I won’t always be looking for speakers and authors who are discovering what we already know. I’m looking for people like Dr. Sinclair, who will stretch us to think in ways we’ve never thought before, to do what we once thought was impossible, showing us that we have powerful reservoirs of mental and physical strength, that we can tap into when needed.  Now that fascinates me and is what will motivate me to keep learning more to share with you here.

With that said, I wanted this week’s Brain Fact Friday to tie into last week’s episode to improve our mental and physical health, since according to a recent survey from the American Psychiatric Association, “almost 70 million adults resolve to find ways to improve their mental and physical health this coming year”[vi] and while looking for ideas, I saw a graphic I created last year that caught my attention. The graphic was about using “hormesis” as a stressor to make us stronger. I know how important hormesis is for our mental strength, by choosing to stretch ourselves beyond what we think we are capable of and had heard of strategies that use hormesis like exposing our body to extreme cold (with ice baths), or extreme heat (with saunas), with exercise, (and HIIT) and even intermittent fasting, but I didn’t know what exactly this stress was doing for me on a cellular level.

What does hormesis or this intermittent stress and adversity do to our cells that makes us physically and mentally stronger?

This brings us to this week’s Brain Fact Friday.

DID YOU KNOW THAT: “We have 2 pathways that are important to longevity—the Sirtuin (the pathway we want to activate for health and longevity) and mTOR System (where too much activity causes disease in the body)[vii]  showing us the importance of understanding the key regulators of ageing and age-related diseases?[viii]

This episode will focus on the Sirtuin Pathway, giving us hope that even when our cells become damaged, the Sirtuins help unwrap and put back together the unraveled, damaged DNA. To me, it’s just like the neuroplastic brain that can also repair itself depending how we live our life, and is refreshing to know that we have tremendous control over our future physical, mental health and well-being, and our resilience to stress.

There are ways that we can naturally boost the Sirtuin genes, opening them up, making them more active, giving us more energy, turning on all our bodies’ natural defenses, and in essence, slowing down the aging process, bringing our attention inside our body, down to the cellular level, helping us to understand why certain hormetic behaviors are good for us, and others that do not involve this stressor, are not.

Dr. David Sinclair, a leading expert in the field of anti-aging reminds us that “our bodies were designed to respond to adversity…and we’ve removed it from our lives because it feels good (or it’s easier)—but we need adversity to be resilient and fight disease.”[ix]

So, this year, as we are looking for NEW ways to boost our mental and physical health, I challenge you to start by thinking of the science behind hormesis, adversity and challenge and stretch our minds to try something new, something that challenges us, makes us uncomfortable (for short periods of time) yet has the potential to yield to outstanding health, and wellness benefits to take us to new heights in the New Year.

Please do consult with your doctor before trying anything new and remember that “you can change your epigenome (our loops of DNA) by how we live our life more than anything our genes give us. 80% is epigenetic (our behaviors and environment can cause changes that affect the way our genes work).” (Dr. Sinclair) I want us to look deeper into why these strategies, that involve some sort of intermittent stress (hormesis) can make us physically and mentally stronger.

Improving the Sirtuin/Longevity Pathway to Reduce Aging by:

Strategy 1: Choosing Workouts That Challenge You

If you have ever hired a personal trainer, it’s not usually because you don’t know what to do, it’s usually the how part that we are missing, the need for someone to push us past where we usually would stop on our own so that we push ourselves enough that to damage our muscle fibers, preparing them to rebuild themselves stronger than they were before.  I did mention on episode #114 that “when we put our body under stress, like we do with exercise, that BDNF (brain-derived neurotrophic factor--which is like fertilizer for the brain) upregulates, triggering the growth of cells to meet the increased mental demands of the movement.”[x]   

When thinking about how to receive the benefits of exercise for improved cognition and well-being, be sure to pick workouts that challenge you, or push you beyond where you would usually stop on your own. “You can choose HIIT (high intensity interval training) where you go all out for 30 seconds to a minute, followed by 15 seconds of rest to experience hormesis. During these intense bursts, your muscles are briefly starved for oxygen, (hypoxia) which stimulates the production of mitochondria (the powerhouse of the cell.)”[xi]  It’s this brief period of stress that “improves the capacity of the cells to withstand greater stress.”[xii]

Strategy 2: Using Saunas, Cryotherapy or Ice Baths

For someone who finds anything below 80 degrees freezing, I’ve not yet tried extreme cold, with ice baths or cryotherapy[xiii] for pain relief, muscle healing, and improving the sirtuin pathway to reduce aging, but many people I know swear by this practice. Until I’m brave enough to try this, I’ll stick to ice-packs, but wonder if you have tried this strategy to speed up healing?  I’ll say that sitting in a sauna is a lot like Arizona summers, and not difficult when you do this often enough to get used to those higher temperatures. The only challenge with this one, is that most of us don’t have a sauna in our home. I remember a friend of mine from Toronto, from Finland, swore by a sauna in his home, and I thought of him when I first heard of using heat stress to “trigger a thermoregulatory response”[xiv] if used regularly. Since I want to make use of the research I discover, I did investigate how expensive it would be to put a small sauna in your home, and Costco[xv] does carry them for a reasonable price. Might be something for next year’s Christmas wish list, or worth saving up for.

Strategy 3: The Benefits of Intermittent Fasting

Pioneer in anti-aging, Dr. Sinclair noticed that “our clock is ticking faster by always being fed…and it’s not important WHAT we eat, but WHEN we eat during the day.”[xvi]

I’ve been practicing this strategy since discovering Jason Whittrock from EPISODE #94[xvii] in 2016 but didn’t understand the science behind fasting back then. Remember that Dr. Sinclair reminded us that “our bodies are designed to respond to adversity” and “when we are hungry, we turn on these adversity, hormetic genes that are called longevity genes—and they make the body fight against aging and diseases,”[xviii] even increasing your mental focus. The problem in America is that most of us don’t allow ourselves to get to the point of hunger where all the benefits are. There are fast food restaurants on every corner to prevent us from starving to death, but I think, this strategy is freeing, giving you so much more extra time and energy that you will never want to give up again once you become free from “needing” to eat. If you want to start this practice, and don’t know where to begin, just skip one meal a day with either breakfast or dinner. No one ever said we “need to eat 3 meals a day” so you’ll notice some paradigms shifting as you try this.

I noticed a marked difference with my health after incorporating this strategy, but it took some time to get used to it. The key is to get past the first 2-3 weeks or so when you think “I need to eat something” and learn to get past the hunger feeling. It does go away. Everyone is different, and so I’ll let you know what works best for me, but that might not work for you. You have to play around these strategies and discover for yourself what will work best for your situation.

I started with fasting Sunday through Wednesday with a 16-hour non-eating window from 5:30pm-9:30am and 8-hour eating window from 9:30am-5:30pm back in 2016. I only drank water, tea or coffee in the non-eating window, and ate fairly clean in the 8 hour eating window, and chose only 4 days a week to do this, so that my body wouldn’t get used to it and adapt.  With time, I began to trust that my body had stores of energy that it would use up, until it was fed or fueled again. It just became my way of life, and who knew it was a longevity strategy! I had no idea.  

I usually exercise early morning with an empty stomach and have never once felt lightheaded or shaky with strenuous exercise on an empty stomach. Just monitor how you feel and adjust this strategy to work for you and your schedule, knowing that over time, your body gets used to whatever you are doing, so you’ll need to continue to switch it up.

Strategy 4: Taking Dietary Supplements (Resveratrol, NMN and Berberine) with Food

Every year I look for what I can add to my health regime to strengthen it and I look for what others are doing in the health and wellness industry. If you’ve been following this podcast for awhile, you will know that I’ve been a longtime fan of Dave Asprey and his bulletproof coffee, so after listening to Dr. Huberman’s podcast[xix], I decided I would try all 3 supplements they discussed (Resveratrol, NMN and Berberine) since both Dr. Huberman and Dr. Sinclair talked about the benefits of each one on health and longevity.

 This strategy I’ve not tried yet, but I put the link in the resource section for these 3 supplements on AMAZON and suggest that you do some research yourself before buying anything.

Aha Moment and Paradigm Shift With This Strategy: Dr. Sinclair mentioned that in the fine print of his study with mice that he gave Resveratrol to, that when they gave this supplement to the mice every day, that the only thing that happened was that the mice were protected against a fatty Western diet. They had no noticeable lifespan extension. But for the mice they gave Resveratrol every OTHER day, they lived over 3 years (which is a long time for lab mice), showing him that there are benefits to NOT taking the same thing every day.  This blew my mind, as I’m a creature of habit, and take the same thing every day. With this research in mind, I’m going to create a new plan of what supplements to take and when. Just like exercise, supplement use needs to be alternated so my body doesn’t get used to what I’m taking.

Just a bit more about the 3 supplements Dr. Sinclair has studied and noted to be anti-aging that I want to try this year:

Resveratrol:  Dr. Sinclair suggests taking 1,000 mg a day that this “must come from a supplement and not from drinking wine, or you would have to drink 200 glasses/day to get the right amount.”  I’m sure we have all heard of the health benefits of resveratrol, that it (may lower blood pressure, has a positive effect on blood fats, lengthens the lifespan of certain animals, protects the brain, may suppress cancer cells)[xx] so I’m going to try it to see what I notice.

NMN: 1000 mg/day Nicotinamide Mononucleotide to protect against heart disease, lower risk of obesity, enhance and maintains DNA repair, and slow down the rate of aging[xxi]  by enhancing NAD levels in the body, an important coenzyme found in all living cells that plays a role in promoting health and prolonging lifespan “but these levels decline as we get older, or obese.”[xxii]  Dr. Huberman and Dr. Sinclair suggested taking 1,000 mg of NMN to fuel the NAD molecule that also fuels Resveratrol to work in the body. It seems this one works best with Resveratrol since it increases those important NAD levels in the body that we need to live, and since numerous studies have demonstrated that “boosting NAD+ levels increases insulin sensitivity, reverses mitochondrial dysfunction, and extends lifespan”[xxiii] I’m definitely going to add this supplement to my health care regime in the New Year.

Berberine: Dr. Sinclair called this the “poor man’s Metformin” Metformin is a drug given to people with diabetes. I used to take metformin for another purpose and had no idea this drug had additional benefits of protecting against heart disease, cancer, frailty and dementia. If you are taking it, then just know there are these additional benefits, and if you don’t have access to it, there’s always Berberine, a powerful supplement with many benefits at the molecular level like “it’s been shown to lower blood sugar, cause weight loss and improve heart health.”[xxiv]

Longevity expert, Dr. Sinclair takes these 3 supplements daily, with a bit of olive oil and vinegar, with a basil leaf, and says it tastes like he’s drinking a bit of salad dressing, which sounds wonderful, but I’ll let you know when I try it out!

To review this week’s Brain Fact Friday:

DID YOU KNOW THAT: “We have 2 pathways that are important to longevity—the Sirtuin (the pathway we want to activate for health and longevity) and mTOR System (where too much activity causes disease in the body) that are key regulators of ageing and age-related diseases[xxv] and we can do things that positively impact the Sirtuin genes, by choosing challenge boosting hormetic activities, opening these Sirtuin genes up, making them more active, giving us more energy, turning on all our bodies’ natural defenses, and impacting the rate of aging.

Whatever strategy we choose (workouts that challenge us, heat/cold exposure, intermittent fasting, or supplements that target anti-aging, my hope is that we now have a different picture of why we are using hormesis to build a better, stronger, more resilient version of ourselves that embraces adversity head on, and full force. Just like when we have peered inside our neuroplatic brain and learned something new on other episodes, we have now looked deep into the longevity of our cells, and understand why hormesis doesn’t kill them, but only makes them stronger!

Have a safe, happy and healthy New Year and I’ll see you next year for the start of Season 7!

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RESOURCES:

NMN (Nicotinamide mononucleotide as an anti-aging health product) August 11, 2011 https://www.sciencedirect.com/science/article/pii/S2090123221001491

NMN Supplement on AMAZON https://www.amazon.com/Nicotinamide-Mononucleotide-Supplement-Metabolism-Capsules/dp/B079S3XF4H

The Science Behind NMN: A Stable, Reliable NAD+ Activator and Ant-Aging Molecule by Christopher Shade Feb. 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238909/#sec1-2title

The mTOR Pathway August 31, 2016 https://www.youtube.com/watch?v=GSx9ryXzCFE

REFERENCES:

[i] Hormesis: Meet the Stress That Makes You Physically and Mentally Stronger Feb. 28, 2021 by Stephanie Eckelkamp https://amp.mindbodygreen.com/articles/hormesis

[ii] https://sinclair.hms.harvard.edu/people/david-sinclair

[iii] Huberman Lab Podcast with Dr. David Sinclair EPISODE #52 https://hubermanlab.com/dr-david-sinclair-the-biology-of-slowing-and-reversing-aging/

[iv] Peter Attia, MD “The Drive” EPISODE #27 with Dr. Sinclair, Ph.D. on “Slowing Aging, sirtuins, NAD, and the epigenetics of aging” Published on YouTube Jan. 6th, 2020 https://www.youtube.com/watch?v=edrIEC0kJv8

[v] The Backlash David Sinclair Faced by the Scientific Community Published on YouTube January 29, 2019 https://www.youtube.com/watch?v=jDdAI-X3y1o

[vi] Neuroscience Meets Social and Emotional Learning Podcast EPISODE #188 on “Putting Mental and Physical Health First” https://andreasamadi.podbean.com/e/brain-fact-friday-on-putting-our-mental-and-physical-health-first/

[vii] The mTOR Pathway August 31, 2016 https://www.youtube.com/watch?v=GSx9ryXzCFE

[viii] Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases by Asmaa Abdullah, Nuraqila Mohd Murshid and Suzana Makpol Published August 31, 2020 https://link.springer.com/article/10.1007/s12035-020-02083-1#:~:text=mTOR%20and%20sirtuin%20are%20key,3).

[ix] Joe Rogan Podcast with Dr. David Sinclair on “How Fasting Can Fight Aging” Published on YouTube June 18, 2021 https://www.youtube.com/watch?v=cUwd-D94pzE

[x] Neuroscience Meets Social and Emotional Learning Podcast EPISODE #114 on “Building a Faster, Stronger, Resilient Brain by Understanding BDNF” https://andreasamadi.podbean.com/e/brain-fact-friday-on-building-a-faster-stronger-resilient-brain-by-understanding-brain-derived-neurotrophic-factor-bdnf/

[xi] Hormesis: Meet the Stress That Makes You Physically and Mentally Stronger Feb. 28, 2021 by Stephanie Eckelkamp https://amp.mindbodygreen.com/articles/hormesis

[xii] Modulating Exercise-Induced Stress: Does Less Equal More? August 1, 2015 by Jonathan M Peake, James F. Markworth https://journals.physiology.org/doi/full/10.1152/japplphysiol.01055.2014?rss=1

[xiii] What are the benefits of cryotherapy https://www.medicalnewstoday.com/articles/319740

[xiv] Saunas for Personal Health and Longevity Strategy by Steve Hill July 22, 2021 https://www.lifespan.io/news/saunas-health-and-longevity/

[xv] 1-2 Person Infrared Sauna from Costco gracia-1-2-person-low-emf-infrared-sauna.product.100675807.html">https://www.costco.com/dynamic-gracia-1-2-person-low-emf-infrared-sauna.product.100675807.html

[xvi] Huberman Lab Podcast with Dr. David Sinclair EPISODE #52 https://hubermanlab.com/dr-david-sinclair-the-biology-of-slowing-and-reversing-aging/

[xvii]Neuroscience Meets Social and Emotional Learning Podcast EPISODE #94 with Jason Wittrock on “Nutrition, Intermittent Fasting, and the Ketogenic Diet”  https://andreasamadi.podbean.com/e/personal-trainer-and-fitness-model-jason-wittrock-on-health-nutrition-intermittent-fasting-and-the-ketogenic-diet/

[xviii] Joe Rogan Podcast with Dr. David Sinclair on “How Fasting Can Fight Aging” Published on YouTube June 18, 2021 https://www.youtube.com/watch?v=cUwd-D94pzE

[xix] Huberman Lab Podcast with Dr. David Sinclair EPISODE #52 https://hubermanlab.com/dr-david-sinclair-the-biology-of-slowing-and-reversing-aging/

[xx] 7 Health Benefits of Resveratrol by Kerri-Ann Jennings March 3, 2017 https://www.healthline.com/nutrition/resveratrol#TOC_TITLE_HDR_2

[xxi] NMN (Nicotinamide mononucleotide as an anti-aging health product) August 11, 2011 https://www.sciencedirect.com/science/article/pii/S2090123221001491

[xxii] Huberman Lab Podcast with Dr. David Sinclair EPISODE #52 https://hubermanlab.com/dr-david-sinclair-the-biology-of-slowing-and-reversing-aging/ 59:25

[xxiii] The Science Behind NMN: A Stable, Reliable NAD+ Activator and Ant-Aging Molecule by Christopher Shade Feb. 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238909/#sec1-2title

[xxiv] Berberine: A Powerful Supplement with Many Benefits by Kris Gunners January, 2017 https://www.healthline.com/nutrition/berberine-powerful-supplement

[xxv] Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases by Asmaa Abdullah, Nuraqila Mohd Murshid and Suzana Makpol Published August 31, 2020 https://link.springer.com/article/10.1007/s12035-020-02083-1#:~:text=mTOR%20and%20sirtuin%20are%20key,3).