Most animals have the latent ability to live longer when stressed. \u00a0It\u2019s called hormesis<\/a>, and it\u2019s a major clue concerning the nature and evolutionary provenance of aging. \u00a0The body compensates when stressed\u2014that\u2019s no surprise\u2014but the remarkable thing is that it overcompensates so that, paradoxically, stress ends up by lengthening lifespan. Sometimes.<\/p>\n One of the prime responses to stress at the cellular level is Heat Shock Proteins, discovered in 1962 in fruit flies. \u00a0Heat was the stressor that led to the original discovery of HSP, and the word \u201cheat\u201d remained with the name, though it soon became clear that HSP are secreted in response to many kinds of stress, including cold. \u00a0HSP 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<\/a>.<\/p>\n HSP protects delicate biomolecules from damage. \u00a0HSP act as chaperones<\/a>, helping newly-created proteins to fold properly, and helping misfolded proteins to find their correct shape. \u00a0HSP protect against sarcopenia<\/a> (muscle-wasting) which is responsible for so much frailty.\u00a0Lab worms with an extra copy of an HSP gene live longer<\/a>. \u00a0\u00a0Here<\/a> is a closely-related finding for fruitflies, but there are contradictory findings for mice [pro<\/a>, con<\/a>].<\/p>\n Heat Shock Factor (HSF) is a signal molecule that turns on the full set of HSP genes. \u00a0It turns on a great many other protective proteins at the same time, a whole library, in fact, of protections. \u00a0\u00a0Calorie restriction<\/a> and exercise both activate HSP, but protein restriction may attenuate HSP. \u00a0HSP induction in response to HSF declines with age in rodents<\/a>, but not if they are calorically restricted. Pro-biotics and high-fiber diets encourage microbiome signaling that increase HSP expression, at least in mice.\u00a0\u00a0Insulin resistance, characteristic of type 2 diabetes, suppresses HSP in response to HSF. \u00a0High fat diets reduce HSP. Garlic in the diet increases HSP.<\/p>\n HSP is neuroprotective<\/a> when there is potential damage from a stroke or head injury. \u00a0Does HSP protect nerves from the slow damage of aging as well?<\/p>\n <\/p>\n Saunas<\/b><\/p>\n In my reading this week, I\u2019ve come to think that saunas may be the second most powerful form of human hormesis after calorie restriction. \u00a0Statistics for saunas suppressing cardiovascular disease and especially dementia make you stand up and take notice. Here\u2019s a clear and straightforward article by Rhonda Patrick<\/a> (FoundMyFitness) about the benefits of saunas.<\/p>\n If you\u2019ve ever run long distances or exercised for endurance, it\u2019s 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\u2019t enjoy getting overheated any more than you do, but hey\u2014stress is stressful. \u00a0How 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. \u00a0The 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. \u00a0Another 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.<\/p>\n \u201cThe greater the discomfort experienced during your workout or sauna, the better the endorphin high will be afterward.\u201d<\/p><\/blockquote>\n Jari Laukkanen, a Finnish cardiologist, followed middle-aged sauna-bathers (men) and matched controls for 20 years. \u00a0His study<\/a> 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. \u00a0A 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. \u00a0An even more impressive number: the Alzheimer\u2019s risk of men taking at least 4 saunas a week was only \u2153 as great as those who took 1 sauna a week.\u00a0 The benefit compared to no saunas at all is likely to be substantially greater yet.<\/p>\n Just this week, there is a new review<\/a> by Laukkanen, author of the above study, who also did much of the the original research in his review.<\/p>\n The review doesn\u2019t mention cancer, and there have been mixed reports whether saunas and HSP in particular protect against cancer or add to cancer risk. \u00a0On 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. \u00a0There is some evidence that saunas enhance the immune system<\/a> and that would likely contribute to cancer resistance. \u00a0In my judgment, the balance of the evidence is that saunas lower cancer risk.<\/p>\n <\/p>\n Choose your poison.<\/b><\/p>\n The body responds to alcohol as a poison, and raises levels of HSP. \u00a0This may be the mechanism by which alcohol consumption (~1 drink per day) lowers heart attack risk<\/a>, though cancer risk is increased even at low doses<\/a>.<\/p>\n I\u2019ve made my choice, and I\u2019ve been a teatotaler my whole life. \u00a0It\u2019s been for personal reasons that I never have written about the established epidemiology of alcohol. \u00a0Moderate alcohol consumption has conventionally been associated<\/a> with a modest increase in life expectancy, (~1 year or less), but conventional wisdom could be wrong<\/a>. \u00a0It\u2019s 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.<\/p>\n <\/p>\n Cold<\/b><\/p>\n HSP is a stress adaptation, not specialized to heat, and in fact cold temperature can also trigger release of HSP. \u00a0That said, cold and heat are not symmetric. Saunas work by raising the core temperature of the body several degrees, as in a fever. \u00a0Cold 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. \u00a0A specific response to cold is a protein called RMB3<\/a>, which promotes neurogenesis.<\/p>\n It\u2019s tempting to take your cold shower or plunge into an icy stream after you\u2019ve been working out and your core temperature is elevated. \u00a0But this may actually cause delayed cramping<\/a> and lessen the benefit of your workout. \u00a0I hate to say it, but after resistance training is the most beneficial time to take your sauna (if the least comfortable). \u00a0If you can\u2019t bear the thought of jumping into a cold shower when your body is already cold, you might try a hot shower first. \u00a0Here\u2019s a study<\/a> that demonstrates a drop in infectious disease rates from hot showers followed by cold.\u00a0 Hof recommends that you take your cold plunge after a course of deep breathing.<\/p>\n 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. \u2014 Rhonda Patrick<\/em><\/p><\/blockquote>\n Does the Wim Hof method increase life expectancy<\/b><\/p>\n In the last several years, Dutch extreme athlete Wim Hof has popularized a training discipline that combines breathing exercises, cold immersion, yoga and meditation.<\/p>\n Wim Hof is able to suppress immune response<\/a> 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. \u00a0When Hof was studied with metabolic and neurologic sensors, the result<\/a> indicated that he has acquired conscious control over physiological adaptations which, in the rest of us, are entirely automatic. \u00a0Is it possible to learn to dial down inflammation by an act of will, or to control our epigenetic age directly from the mind?\u00a0 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. \u00a0There have long been stories about yogis<\/a> 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.<\/p>\n There is no direct evidence that Wim Hof training affects aging. \u00a0Indirect 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 \u00a0I\u2019m eager to see if Wim Hof method has an effect on methylation age, and will include it in the Data BETA study<\/a> that is ramping up this fall (DataBETA is the name I\u2019ve chosen for the Mother of All Clinical Trials. \u00a0It stands for Database for Epigenetic Evaluation of Treatments for Aging.)<\/p>\n <\/p>\n The Bottom Line<\/b><\/p>\n If the Finnish review<\/a> is to be believed, then hyperthermia\u2014overheating\u2014is one of the most powerful modes of hormesis we know of, ranking second only to calorie restriction. \u00a0Just 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<\/a>) and from calorie restriction (or fasting). \u00a0In other words, combining low calorie with high heat might, if we\u2019re lucky, yield life extension equivalent to the sum of the two measures separately. \u00a0Cold exposure and the full Wim Hof program, including meditation techniques, show promise, but are further from validation as a life-extending practice.<\/p>\n","protected":false},"excerpt":{"rendered":"
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