Heat Shock Protein
[My sources for much of this article are a 2018 review from University of Campinas, Brazil and a 2016 review on hormesis by Joan Smith Sonneborn, as well as the ever-inspiring and accessible summaries by Rhonda Patrick.]
Most animals have the latent ability to live longer when stressed. It’s called hormesis, and it’s a major clue concerning the nature and evolutionary provenance of aging. The body compensates when stressed—that’s no surprise—but the remarkable thing is that it overcompensates so that, paradoxically, stress ends up by lengthening lifespan. Sometimes.
One of the prime responses to stress at the cellular level is Heat Shock Proteins, discovered in 1962 in fruit flies. Heat was the stressor that led to the original discovery of HSP, and the word “heat” remained with the name, though it soon became clear that HSP are secreted in response to many kinds of stress, including cold. HSP are not a single protein, but a family of molecules, all of which are highly conserved; the human versions are remarkably similar to HSP in flies and even yeast cells.
HSP protects delicate biomolecules from damage. HSP act as chaperones, helping newly-created proteins to fold properly, and helping misfolded proteins to find their correct shape. HSP protect against sarcopenia (muscle-wasting) which is responsible for so much frailty. Lab worms with an extra copy of an HSP gene live longer. Here is a closely-related finding for fruitflies, but there are contradictory findings for mice [pro, con].
Heat Shock Factor (HSF) is a signal molecule that turns on the full set of HSP genes. It turns on a great many other protective proteins at the same time, a whole library, in fact, of protections. Calorie restriction and exercise both activate HSP, but protein restriction may attenuate HSP. HSP induction in response to HSF declines with age in rodents, but not if they are calorically restricted. Pro-biotics and high-fiber diets encourage microbiome signaling that increase HSP expression, at least in mice. Insulin resistance, characteristic of type 2 diabetes, suppresses HSP in response to HSF. High fat diets reduce HSP. Garlic in the diet increases HSP.
HSP is neuroprotective when there is potential damage from a stroke or head injury. Does HSP protect nerves from the slow damage of aging as well?
Saunas
In my reading this week, I’ve come to think that saunas may be the second most powerful form of human hormesis after calorie restriction. Statistics for saunas suppressing cardiovascular disease and especially dementia make you stand up and take notice. Here’s a clear and straightforward article by Rhonda Patrick (FoundMyFitness) about the benefits of saunas.
If you’ve ever run long distances or exercised for endurance, it’s intuitive that increased body temperature will eventually induce strain, attenuate your endurance performance, and accelerating exhaustion. What might not be as intuitive is this: acclimating yourself to heat independent of aerobic physical activity through sauna use induces adaptations that reduce the later strain of your primary aerobic activity. Hyperthermic conditioning improves your performance during endurance training activities by causing adaptations, such as improved cardiovascular and thermoregulatory mechanisms.
I don’t enjoy getting overheated any more than you do, but hey—stress is stressful. How surprised can we be that heat is a powerful inducer of Heat Shock Protein? Perhaps more interesting is that saunas are associated with increased growth hormone, a far safer and cheaper way to achieve higher HGH levels than injections. The combination of HGH and HSP help to maintain muscle mass against the erosion that almost always comes with age. Patrick documents that saunas contribute to maintaining (or restoring) insulin sensitivity, and to growth of new brain cells. Another pathway by which saunas work their magic is norepinephrine=noradrenaline, which is both a neurotransmitter and a hormone, and higher levels are associated with good attention and cognitive performance.
“The greater the discomfort experienced during your workout or sauna, the better the endorphin high will be afterward.”
Jari Laukkanen, a Finnish cardiologist, followed middle-aged sauna-bathers (men) and matched controls for 20 years. His study found dramatic decreases in cardiovascular deaths, and a 40% drop in all-cause mortality for those reporting sauna use at least 4 times per week for 20 minutes. A prospective study–planned in advance to follow 2,300 men over 20 years–is the gold standard for epideiology. A 40% drop in mortality is worth about 3 years of extended life. An even more impressive number: the Alzheimer’s risk of men taking at least 4 saunas a week was only ⅓ as great as those who took 1 sauna a week. The benefit compared to no saunas at all is likely to be substantially greater yet.
Just this week, there is a new review by Laukkanen, author of the above study, who also did much of the the original research in his review.
The review doesn’t mention cancer, and there have been mixed reports whether saunas and HSP in particular protect against cancer or add to cancer risk. On the one hand, localized applicatation of heat and even whole body heat are a well-established cancer treatment over 40 years. On the other hand, HSP increases the ability of cells to survive stress, and that includes cancer cells. There is some evidence that saunas enhance the immune system and that would likely contribute to cancer resistance. In my judgment, the balance of the evidence is that saunas lower cancer risk.
Choose your poison.
The body responds to alcohol as a poison, and raises levels of HSP. This may be the mechanism by which alcohol consumption (~1 drink per day) lowers heart attack risk, though cancer risk is increased even at low doses.
I’ve made my choice, and I’ve been a teatotaler my whole life. It’s been for personal reasons that I never have written about the established epidemiology of alcohol. Moderate alcohol consumption has conventionally been associated with a modest increase in life expectancy, (~1 year or less), but conventional wisdom could be wrong. It’s always difficult to separate variables in large population studies, and alcohol consumption is linked to so many different factors, all of them more powerful influences than alcohol itself.
Cold
HSP is a stress adaptation, not specialized to heat, and in fact cold temperature can also trigger release of HSP. That said, cold and heat are not symmetric. Saunas work by raising the core temperature of the body several degrees, as in a fever. Cold is applied on the skin, and the core of the body works harder to keep its temperature close to normal. The benefit is mediated by the cold-sensing nerves in the skin, which trigger release of norepinephrine, similar to heat exposure. A specific response to cold is a protein called RMB3, which promotes neurogenesis.
It’s tempting to take your cold shower or plunge into an icy stream after you’ve been working out and your core temperature is elevated. But this may actually cause delayed cramping and lessen the benefit of your workout. I hate to say it, but after resistance training is the most beneficial time to take your sauna (if the least comfortable). If you can’t bear the thought of jumping into a cold shower when your body is already cold, you might try a hot shower first. Here’s a study that demonstrates a drop in infectious disease rates from hot showers followed by cold. Hof recommends that you take your cold plunge after a course of deep breathing.
One of the most consistent and profound physiological responses to cold exposure is a robust release of norepinephrine into the bloodstream, as well as in the locus coeruleus region of the brain. — Rhonda Patrick
Does the Wim Hof method increase life expectancy
In the last several years, Dutch extreme athlete Wim Hof has popularized a training discipline that combines breathing exercises, cold immersion, yoga and meditation.
Wim Hof is able to suppress immune response to a standard challenge, suggesting he is also able to consciously suppress the auto-immune response that contributes to arthritis, and probably diabetes and AD as well. When Hof was studied with metabolic and neurologic sensors, the result indicated that he has acquired conscious control over physiological adaptations which, in the rest of us, are entirely automatic. Is it possible to learn to dial down inflammation by an act of will, or to control our epigenetic age directly from the mind? This is an approach to health and perhaps to anti-aging that has always fascinated me, though there is little in the mainstream literature on the subject because it is presumed impossible. There have long been stories about yogis and ascetic devotees of Eastern religions who culture extraordinary control over their bodies and live to extraordinary ages. Of course, we would like to see these claims subjected to controlled conditions and standardized lab tests, but there are probably good reasons why most ascetic hermits have no interest in taking leave from their mountain caves to serve as lab rats.
There is no direct evidence that Wim Hof training affects aging. Indirect evidence is that it lowers inflammation, which makes a large contribution to all the diseases of old age, and that it releases norepinephrine and RMB3, both of which are neuroprotective I’m eager to see if Wim Hof method has an effect on methylation age, and will include it in the Data BETA study that is ramping up this fall (DataBETA is the name I’ve chosen for the Mother of All Clinical Trials. It stands for Database for Epigenetic Evaluation of Treatments for Aging.)
The Bottom Line
If the Finnish review is to be believed, then hyperthermia—overheating—is one of the most powerful modes of hormesis we know of, ranking second only to calorie restriction. Just as interesting is the fact that hyperthermia works by a path independent of insulin, so we might hope that there is synergy between saunas (or Bikram yoga) and from calorie restriction (or fasting). In other words, combining low calorie with high heat might, if we’re lucky, yield life extension equivalent to the sum of the two measures separately. Cold exposure and the full Wim Hof program, including meditation techniques, show promise, but are further from validation as a life-extending practice.
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I was skeptical at first, but now I’m really buying into the power of saunas. The cardiovascular benefits are real and anything that improves immune surveillance almost certainly will help in cancer prevention.https://www.jstage.jst.go.jp/article/biomedres/36/2/36_135/_pdf
It also strikes me that we have evolved to undergo cycles of anabolism and catabolism so I’m starting to think that we’ll find out that IF is > CR, just as cycling rapamycin is superior to daily use.
We also need to carefully evaluate the contribution of red, infrared, and other light on the skin, to these factors. There is a reason good saunas allow Near Infrared to hit your skin. You don’t get the same impact wearing a neoprene wetsuit that may get your body up to the same temperature over time. Much is known about red light and healing… doubling wound healing speed according to NASA/ US Navy experiments. I’m concerned the hysteria about melanoma is causing light deficient people to get less. If your Vitamin D (a steroid) is low every time you visit the doctor– fix that! Insufficient vitamin D causes 30 times the health damage of melanoma.
It is hard to read and lacks succinct summaries, but I think the “con” study concerning HSP and health involved lifelong HSP overexpression in the mice. Is there a reason to think that this is the same as occasional spurts of HSP that accompany a few sauna each week? I have no data, but seriously doubt that living in a sauna would increase lifespan. The right test is probably to give wt mice saunas at a rate and length comparable to humans taking two, three, four, five and six 20-minute saunas per week. Give half of each sub-group a cold dip afterward, and then we will have a very worthy baseline from which to design human experiments, perhaps using volunteers in prison, many of whom would surely jump at the chance for such a regime, especially if it also accelerated their release date.
Good proposal, with the understanding that mice are so much smaller that they would cook if left in a 180 degree sauna for 20 minutes, which might be the right intensity for an adult human.
Is there any difference in outcome between dry saunas and steam rooms that you have read about?
My guess is that dry heat and wet heat would have the same effect, and the benefit comes from raising your core temperature, but I’m pretty sure no one has done the study.
what about a hot tub? It would raise core temp too, right?
I offer my non-peer-reviewed, allegorical knowledge about this matter, based upon decades of being a lover and frequenter of sauna, etc. I cock my head sideways at Josh’s dislike of them, as I actually enjoy and look forward to my sauna time.
Suana is hotter than steam room, which is hotter than hot tub, because water transfers heat faster than steam (at the same temperature), which transfers heat faster than dry air. …But, in my experience, most saunas are not completely dry. I know this because I routinely read in the sauna, and my glasses fog up badly until they approach the room temperature.
Users often believe that steam is better for your lungs, as it is alleged to loosen sticky mucous. That is not unreasonable, but I think it might be found exaggerated or untrue if actually tested. I like dry suana the most, mainly because it is the most sanitary option for penurious dogs like me who are reduced to using semi-public facilities. Dry saunas are held at well above 150F, so most everything that would infect you is dead. Steam rooms often have a tell-tale stink, and hot tubs are not only loaded with dubious chemicals, but are often slightly yellow and leave me feeling itchy if I don’t scrub myself afterward with soap. Also, unlike steam and hot tub, you can more easily adjust the temperature in a dry sauna by simply climbing to a higher or lower seat. Plus, only in a dry sauna can you reasonably read a magazine.
For whatever reason, regular users can generally stand the heat for a lot longer than novices. In the small sauna/steam-room at my gym, numerous people will often come and go during my stay in there, and even then, I leave as much from boredom as having reached my limit.
I have a queer habit in the sauna that serves me well, and am old enough that I don’t care about funny looks from others. I take a stiff-bristled utility brush, and scrub every exposed piece of skin near the end of my stay. Yes, it hurts slightly, but it leaves me feeling great afterward, and I fancy that the non-injurious stimulation is good for skin. Don’t take my word – try it!
WARNING: I forgot to mention a depletion of electrolytes associated with frequent use of hot tubs/rooms, which can’t be really good. A quick look from your browser will confirm this in spades. On a personal note, I sometimes suffer from longevity-linked leg cramps at night, and the problem is both more common and more intense if I sauna without supplementation afterwards. A simple banana seems to help me quite a bit.
On the brighter side, and perhaps related to the benefits of sauna, they result in a concentrated outflow of heavy metals in your sweaty. See, for example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312275/
… or hot tubs, for that matter. Much more comfortable IMO than saunas. Especially when there’s a snow or windstorm raging around you. In the former, you can make like the Finns and go roll in snow, as well. Plus, if your hot tub is ozone purified….
How long should the sauna last to be most effective?
The main thing is: Don’t risk passing out or hurting yourself. You’ll start to get uncomfortably hot and lethargic. Your heart will start racing. Don’t stay too much longer after that.
In Laukkanen’s study, 20 minutes was more effective than 11 minutes. Take 20 min at 180 to 200 degrees as an upper limit.
Any body have ane thoughts on Infra Red Saunas ..?
I use one daily as part of my 6 monthly low calorie 7 day fast
The programme also includes daily massage and exercise
I like your suggestion of post sauna scrub
This reminds me of a Chinese scrape treatment which can Best Dermot very vigorous but apparently immune stimulating
Wim Hof. That dude looks like he listens to Johnny Cash while ripping the lid of a bottle of Jack Daniels with his teeth – No doubt he has been repeatedly dropped off at the North-pole in his underwear as a Navy Seal or Green Beret for winter-warfare training. He’s probably thinking about fighting Chuck Norris.
I wonder whether a phenomenon that you’ve mentioned many times before is relevant here: overlap. For instance, exercise induces heat shock proteins (https://scholar.google.com/scholar?hl=en&as_sdt=1%2C5&q=exercise+heat+shock+protein&btnG=&oq=exercise+heat+sh) If someone were fit and exercised regularly, how much extra benefit do saunas or cold exposure bring to the table?
There are other examples in anti-aging. Would metformin help those who are lean and insulin-sensitive? It’s associated with lower mortality, but we all know what the average person’s health status is like.
We’re always told that polyphenols in vegetables, fruits, coffee, tea, and wine are good for us, and one of the main reasons is that they upregulate the Nrf2 transcription factor for antioxidant defense. But again, exercise upregulates Nrf2.
Also, by the way, increased cancer risk reported in light to moderate drinking may be substantially due to underreporting of intake, i.e. an artifact. https://link.springer.com/article/10.1007/s10552-014-0372-8
We are always told that polyphenols in vegetables, fruits, coffee, tea, and wine are good for us, that’s why people do not want to find more effective anti-aging products. I prefer synthetic chemicals that Denham Harman discovered in 1956. They extend life by 100% to 200%.
Harman also discovered that polyunsaturated fatty acids including omega 3 accelerated aging. Well, you see, and they are such a favorite food that is referred to as beneficial. But it has a beneficial effect on health insurance companies only.
The large Finnish study took into account exercise as a possible confounding factor, along with many others:
“age, body mass index …, systolic BP, … cholesterol level, smoking, alcohol consumption, previous myocardial infarction, type 2 diabetes mellitus, CRF level, resting heart rate, physical activity, and socioeconomic status”
From:
https://www.mayoclinicproceedings.org/article/S0025-6196(18)30275-1/fulltext#sec2.2
So it seems to be a separate effect, which is great news.
Turns out there is a study directly addressing this question, which seems to be based on the same data set, with authors in common:
https://www.ncbi.nlm.nih.gov/pubmed/28972808?dopt=Abstract
If I’ve got my math right, it looks like frequent sauna use provides another ~16% risk reduction for CVD/mortality, even if you have good cardio fitness level already.
Whether the effects on dementia are also independent doesn’t seem to have been addressed.
Regarding cancer and fever
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312698/#!po=62.0000
In the days before chemo, fever was sometimes induced in cancer sufferers through intentional infection. And miraculous cures sometimes resulted.
Anytime I use the sauna regularly, my sleep/breathing/heartbeat all go off… Not sure there is a large benefit in people who already activate HSP by exercise or other means. Plus, in those with stress axis issues, it might be a negative.
Might be linked to electrolyte/mineral depletion, as mentioned above.
That’s okay, so it’s supposed to be. When you add minerals such as sodium, potassium, lithium and magnesium, you will fall asleep easily without premature waking. And your heart pounding will disappear.
Can’t afford a sauna, could I just sit in a hot car for 20 minutes a few times a week during the summer? Also need a winter plan, how long and how cold, should I be wet?
A hot car works perfectly well for heat shock. I have also tried shutting all the windows, turning on all of the lights, the oven, the clothes dryer, and my television sets … the room only got a couple of degrees warmer though and it took a really long time – I’m not convinced that this is not a viable option though – still working on some of the details and I’m not one to give up easily.
In winter for cold shock immediately upon awakening go straight outside naked (for maximum effect) or with only underwear on (for rookies/wimps); roll around on the ground or make snow angels (I love making angels). Start out doing this dry. Once you have perfected this you can start to dump water on your head first – but only do this when you’re outside silly!!! One time I forgot and poured the water right on my head inside the house and boy oh boy did my wife get mad at me!!!
Hi Roger!!!
Are you thinking about getting wet and going outside??
I did this and my feet froze to the ground and I was stuck in one spot for days until I realized I could pee on my feet to heat them up and break free.
Josh I read this with interest. But a feeling of deprivation as there are no saunas in the regional town where I live in Australia…
But then I got thinking..What about electric blankets ? Here in Oz most homes are NOT centrally heated as in the USA & Canada..So bedrooms tend to be cold in Winter as it’s been for the past 3-4 months here. And so I use the electric blanket every night over Winter and fall asleep with it on and then wake up after an hour or so sweaty and hot..
Any thoughts ?
One-person heat box
Expensive Josh.. And does not respond to my query re using an electric blanket to get the same effect.
Sure – try the electric blanket and see how hot you can get yourself. There are many ways to cook a cat. Has Bikram Yoga come to Oz?
Yes, well I’ve been doing it for months each Winter for about 10 years…And feeling good so far, !
Re Bikram, I’ve heard of it..But never seen it in action or felt the need to try it either..
Regarding heat and cancer;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312698/
In the days before chemo, cancer patients were sometimes intentionally infected, sometimes with miraculous results.
The idea is that the resulting fever recruits macrophages into the area, and whilst there, they attack the cancer.
A human being is part of the whole called by us the ‘Universe’; a part limited in time and space.
He experiences himself, his thoughts and feelings as something separate from the rest — a kind of optical delusion of his conciousness.
The striving to free oneself from this delusion is the one issue of true religion.
Not to nourish the delusion but to try to overcome it is the way to reach the attainable peace of mind.
Hi Josh,
I have a question fo you since you have read and know a lot about this.
Can an organism in severe starvation mode develop cancer ?. There are some studies that shows that starvation mode is beneficial for reducing cancer.
But I found no study in which some organism (for example rats) in starvation mode can develop cancer
Cancer needs food, same as other cells, only more so. Problem is, you gotta eat. And once you’ve got cancer, starvation isn’t guaranteed to do more than stop it growing.
Starvation does sensitize the cancer cells to chemotherapy ; so much so that it will one day be a standard part of the protocol. The days of patients in cancer wards being fed ensure to keep their weight up will soon be over.
Of you found out you had cancer tomorrow (God forbid), what woukld you do in addition to standarrd therapies like chemo, Paul?
Of course you can’t stop the little bastard cells from growing, so the aim is to sensitize them to the generalized and non specific poisons that we employ to kill them ( and healthy cells as well unfortunately).
The most studied to date are CBD oil, ldn, and prolonged fasting periods. They all hold some real promise. This field seems to be evolving rapidly and turmeric may also be helpful.
I might jack up my rapamycin. Not sure.
Paul – from your lips to the Medical Establishment’s ear.
I made an interesting discovery. When you eat 1 tablet of 5 mg Li-orotate in the half of the sauna, you can take the heat relaxed and enjoyable. You then have the desire to have sex right after the sauna.
Is that a good thing?
Depends whose in there with you, lol.
In addition, you will sweat out some of the cadmium in accumulated in your body
Excellent article!
A couple of points:
The temperature gauges in saunas are very frequently ‘adjusted’ to over-read, so as to save electricity for the operator and prolong the life of the equipment.
Most people have difficulty staying in a 80-90 degree Celcius sauna for more than 15-20 minutes. I can barely manage 20 minutes, after two years of 3 to 4 sauna’s a week.
I vaguely recall reading some research that said steam actually feels much hotter than a dry sauna, if both are at the same temperature, so steam rooms will probably feel hotter but not raise core temperature as a dry sauna does.
Dry sauna lowers my BP and blood sugars.
I can’t imagine (but stand to be corrected) that any hot tub could emulate how I feel (or have the health benefits) in a sauna. It’s so hot I can’t wait to get out!
Upon reading the sauna study research years ago, my husband made a very cost effective near infrared light sauna board with 5 250 watt lights used in chick breeding and old fashioned bathroom heat lamps. We used the internet provided model for safety (sort of) but changed the configuration to up and down instead of diamond shaped to reach more of our bodies with the light.
One can use a tile or concrete shower with at least 4 feet by 3 feet space (depending on your size) to set this up or construct a wood box or buy a used sauna cheaply on line to get the “cabin”. Smaller is better to achieve the heat with one light board and not to need two electricity sources. However, building two light boards will achieve the required heat more swiftly of 170 or 175 degrees or more F safely. You can use two if your electrical sources are strong enough to be safe or if you use extension cords to draw in from various breakers, which often max out at 1500 watts each.
We have used this single light board in several settings including a small closet. You can be inventive with how to set it up including making a built up box if you have no built in drains to use.
Buy the silver aluminium foil quilted insulation roll(s) to line the enclosure of the shower stall or inside of the box for less heat loss and less electricity usage. Made us not have to build the second board to get up to 180 degrees F and have to find more insulatable space with a drain for the sweat.
This was made for less than $400 about 5 years ago. Still works well and doesn’t look bad either. (Replaced lights twice, however, due to infrared quality “giving out” worries, not because the bulbs burned out. Determining how to measure this near infrared light quality was beyond our ability to figure out. So we hope this is sufficient.)
We feel better (anecdotal, but nice) when we take the sauna 3 to 5 times a week 20 minutes. We use a kitchen timer and oven thermometer, not scientific quality, but seems adequate. We checked it with a higher cost manufacturing facility thermometer twice and found them to be within 5 degrees after 12 minutes. We feel ESPECIALLY great if we can get into an ice bath after a quick shower after the sauna–though we are not sure, we maximize HSP positive effects on longevity, We do not pair saunas usually with intense exercise.
We have been without the sauna as we traveled this summer and are experiencing less feeling of well being and energy and more aches and pain and less good sleep. PS A horse or animal trough can be used for the ice bath, we have seen on the internet recently, but we don’t have one.
Everyday, I take first a hot, then a cold, shower and now find it pleasant and slightly uncomfortable if I don’t get the cold part. >__?
Long post, apologies.
How much of the CV protective effect of saunas is related to nitric oxide release in the skin?
If so, possibly cold would not have the same effect.
Also, advantages in Finnish study might disappear in people at lower latitudes with more exposure to sunlight which also triggers NO release from the skin. Would guess exercise itself might also produce the same.
Possibly L-citrulline could have a similar effect.
Question would be whether there is an independent anti-aging effect apart from the NO effect.
There is a cultural/psychological side to this. In Scandinavian sauna’s people are in the nude, at the least in ‘the cabin ‘ but very often also outside of that. Socializing with your boss, your colleague or your mother in the nude is just normal and takes away much of the stress caused by day to day social constraints. It’s just hard to have a grudge against someone you meet in the nude, so that’s good for your BP etc….
The picture above is probably taken in US or UK because the depicted are dressed in swimming gear! Did they expect to swim inside the cabin? 🙂 A repeat research in the USA might give totally different outcomes…