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Heat Acclimation Benefits from Hyperthermic Conditioning and Active Thermal Exercise

Introduction

Research has shown heat acclimation can cause substantial improvements in the physiology of body and brain, similar to the enhancement of aerobic performance which occurs from altitude acclimatization.

Hyperthermic conditioning is passive exposure to high temperature and “Active Thermal Exercise” (“ATE”) includes cardiovascular (aerobic), strength or flexibility exercise performed in high temperature environments.

Exercise in heat, as compared with an ambient-neutral environment, causes   changes in the dynamics of the human body, including alterations in the the circulatory, thermoregulatory and endocrine systems.(32) A number of interrelated physiologic processes work in concert to keep the core temperature stable, maintain central blood pressure and muscular function , and regulate fluid volume.(32)

The numerous physiological gains from heat acclimation include reduced oxygen uptake, muscle glycogen sparing, reduced blood lactate levels, increased skeletal muscle force generation, plasma volume expansion, improved myocardial efficiency, and increased ventricular compliance.

Studies have established that the effect of controlled passive high heat exposure and/or exercise done in a controlled high heat environment stimulates a number of physiological changes which result in multiple benefits including the following:

  1. Heat Acclimatization/Acclimation
  2. Cardiovascular Changes
  3. Biochemical Changes
  4. Benefits for the Brain
  5. Benefits for the Muscles
  6. Improved Body Composition
  7. Greater LongevityHEAT ACCLIMATIZATION/ACCLIMATION

Acclimatization (or acclimation) is the process by which the human body makes physiologic adaptations to reduce the stress of an environment. (31) Heat acclimatization refers to an organism’s ability to survive an otherwise lethal heat stress from a prior heat exposure sufficient to cause the cellular accumulation of heat shock proteins.(24) Studies have shown that a period of 9 to 10 days is generally sufficient to attain most of the physiologic benefits associated with acclimatization,(31)  and that physical endurance for exercise in hot, dry environments appears to be limited by the attainment of a critical level of core temperature.(5) High core temperature– and not circulatory failure or metabolic depletion– is the critical factor in heat stress, both before and after acclimation (5) Heat acclimatization results from a series of elevations in core temperature, generated by performing work in the heat, (24) and results in a number of physiological changes including the following:

  1. Improved thermo-regulatory control: Thermoregulatory control is improved via activation of the sympathetic nervous system and the resulting increases in the flow of blood to the skin and the rate of sweating.(2) Acclimatization to work in the heat brings an earlier onset of sweating, increase in sweat rate and evaporative cooling that reduces heart rate in proportion to decreased core temperature.(2,45) After acclimation, sweating occurs at a lower core temperature and the sweat rate is maintained for a longer time period.(2)
  2. Reduced resting core temperature and greater heat-dissipating capacity: Heat exposure causes a cascade of cardiovascular adaptations to heat including higher heart rates.(33) Heat acclimation reduces resting core temperature and increases heat-dissipating capacity. (24) Heat acclimation has also been shown to increase stroke volume, plasma volume (by 13%) and sweat rates.(5,29,32)
  3. Greater ability to dissipate excessive body heat and maintain lower core temperature: ATE lengthens the time before the core temperature reaches 40 degrees C.(1) The resulting improvements in evaporative cooling enhances the dissipation of metabolic heat during exercise in heat.(29)
  4. Prolongs ability to continue exercising before exhaustion: Trained athletes generally reach the point of exhaustion when core temperatures reach 39 degrees Celsius.(34) Heat acclimatization allows the organism to tolerate a higher core temperature and therefore prolongs the ability to continue exercising before exhaustion. (24) A study using a climatic chamber to study exercise in dry heat found that acclimation increased average endurance before reaching exhaustion of the study subjects from 48 minutes to 80 minutes.(5)
  5. Reduced lactate accumulation: Studies have also shown that heat acclimation results in reduced lactate accumulation in blood and muscle.(3)
  6. Results in increased intracellular heat shock proteins (HPS): HSPs are involved in maintaining cellular protein conformation and homeostasis during stress.(23, 24). The increase in HSPs resulting from heat acclimation is illustrative of a cellular adaptation to repeated heat stress in humans.(23)

 CARDIOVASCULAR CHANGES

Exercise- and heat conditioning- cause the core temperature to increase. To cool the body, blood is sent to the skin to transfer the heat from the core to the skin. The process of perspiration causes evaporation from the skin to cool the blood before it is returned to the core.(29)  This process is called “thermo-genesis” and results in increased heart rate, stroke volume  and cardiac output at any given exercise intensity.(29) In sufficiently hot and/or humid environments, the process occurs even without exercise.  If heat is not dissipated, the core temperature will increase and the subject will experience fatigue and exhaustion.(29) Exercise combined with heat exposure increases body temperature and  activates beneficial physiological responses more significantly than either exercise or heat alone.(32)

Cardiovascular improvements which help to maintain a stable core temperature include the following:

  1. Increased stroke volume: The amount of blood pumped by the left ventricle of the heart in a single contraction. Increased stroke volume reduces cardiovascular strain and lowers the heart rate for the same given workout.(2) Exercising in heat causes acclimation and increases stroke volume more than just exercise or heat exposure alone.(5,32)
  2. Increased heart rate and cardiac output: ATE can increase heart rate up to 100 beats per minute with moderate heat exposure and/or exercise intensity and up to 150 beats per minute with high heat exposure and/or exercise intensity.(97) Cardiac output is also increased with ATE.(29) Exercising in a hot environment increases cardiac output more than just exercise or heat exposure alone.(32) Studies have shown that hyperthermic conditioning causes rises in cardiac output proportionally to increase in heart rate, and can increase cardiac output. by as much as 75%! (108)
  3. Increased sweating rate: The rate of sweating is increased with both exercise and heat exposure. A study with 12 fit subjects exercising to exhaustion at 95 degrees F. (and 87% relative humidity) showed a 26% increase in sweating rate.(91) Heat acclimation increases the size of the eccrine sweat glands — and larger glands produce more sweat.(41) Thermal exposure combined with exercise results in greater increases in sweating than passive heat exposure alone.(32) Exercising in heat can cause sweat loss of from 2 to 6 pounds (1 to 3 liters) per hour, and each vaporized liter of sweat extracts 580 calories from the body! (29)
  4. Increased sweat sensitivity: Sweat sensitivity determines the body’s potential for evaporative cooling.(6) Sweat sensitivity increases during both heat acclimation and exercise conditioning.(32)
  5. Increased core temperature: A rise in core temperature triggers the body’s temperature regulating center for heat dissipation. Numerous studies have shown that exercise in hot, dry environments is limited by the attainment of a critical level of core temperature and that high core temperature, not circulatory failure or metabolic depletion, is the critical factor in heat stress.(5, 121)
  6. Increased blood flow to muscles: ATE increases the flow of blood to the skeletal muscles which keeps them fueled with glucose, fatty acids, and oxygen. At the same time, metabolic by-products such as actic acid are more effectively removed. Improved delivery of nutrients reduces muscles dependence on glycogen stores, which helps endurance athletes perform for longer periods.
  7. Increased blood plasma volume and red blood cell count (RBC): ATE has been shown to increased blood plasma volume by as much as 7.1% (13% in another study(5)) and increase red blood cell count (RBC) by 3.5%.(1) Increases in RBC results in increased the delivery of oxygen to the muscles.
  8. ATE reduces muscle glycogen use: Studies have shown that ATE reduces muscle glycogen use by 40 to 50% before heat acclimation.(7,8) It is believe that reduced muscle glycogen use results from the increased flow of blood to the muscles.(7)
  9. Enhanced endurance: The cardiovascular improvements described above have been shown to enhance endurance in both trained and untrained test subjects.(2,3,4) Heat acclimatization allows the organism to tolerate a higher core temperature and therefore prolongs the ability to continue exercising before exhaustion. (24) A study using a climatic chamber to study exercise in dry heat found that acclimation increased average endurance before reaching exhaustion of the study subjects from 48 minutes to 80 minutes.(5)

III.BIOCHEMICAL CHANGES

  1. Reduced rate of glycogen depletion: When glycogen levels are low, muscles use protein and amino acids to produce glucose.(29) Protein and amino acids are the building blocks of muscle.(29) With shortages of glycogen, muscle starts using vital protein and amino acids for energy purposes.(29) This leads to muscle damage and overtraining (it has been shown that muscle damage limits and interferes with glycogen storage and synthesis). (29) Glycogen is the storage form of glucose + carbohydrates. About 80% of total carbohydrate is stored in skeletal muscle (about 14% is stored in the liver and 6% in the blood in the form of glucose).(29) Glycogen is important but humans have a limited capacity to store it.(29) Muscle glycogen is crucial for ATP re-synthesis during exercise.(29) Studies show that exercising in hot environments reduces muscle glycogen use by 40 to 50% and show reduced rates of glycogen depletion due to improved muscle perfusion.(7,8). Additional studies show that heat acclimation leads to sparing of muscle glycogen associated with enhanced ability to perform highly intense exercise following prolonged exertion in the heat.(7)
  2. Increased release of human growth hormone* (HGH): HGH is a vital hormone that affects the muscle loss and atrophy that typically occurs with aging.(12,13) The higher your levels of HGH, the healthier and stronger you will be. For most people, at about the age of 30 a stage called “somatopause” is reached. When this point is reached, HGH levels begin to drop off dramatically. This decline in HGH levels contributes to the aging process, so the maintenance of high HGH levels is increasingly important as we age.(43) A study has shown that exercise in a warm environment induced significant elevations in HGH concentrations (exercise in induced elevations of plasma HGH levels with increments exceeding 20 ng/ml in 29 degree C. water and 30 ng/ml in 36 degree C. water).(68)

Studies have documented that hyperthermic conditioning can significantly induce the release of human growth hormone (HGH). (68,11,12,13) One study showed a doubling of HGH levels with only two 20-minute heat sessions at 176 degrees F.(11,12)  A second study showed that HGH levels can be increased fivefold with only two 15-minute heat-conditioning sessions,(11,12) and a third study showed that two one hour heat sessions each day at 176 degrees F. for one week increased HGH levels by sixteen times on the third day.(13) When hyperthermia and exercise are combined, the synergistic effect causes even greater increases in HGH.(93)

  1. Increased protein synthesis: Stimulation of the uptake of amino acids into muscle cells increases protein synthesis. Exercise in heat has been shown to contribute to improved protein synthesis.(11,14,15)
  2. Inhibited cellular protein degradation (and enzymes responsible for same): Hyperthermic conditioning and exercise in heat contribute to improved regulation of protein metabolism.(11,14,15,18)
  3. Reduced blood lactate levels: Reduced lactate levels result from incomplete glucose burning because the cardiovascular system cannot furnish enough oxygen to break down pyruvic acid). Pyruvic acid is converted to lactic acid. (29) Increased levels of lactate in muscles causes fatigue during exercise. Reduced lactate production can increase the capacity for prolonged physical activity (it is believed that this is because of the increased blood flow to the muscles). (29) Exercise performed in a hot environment has been shown to reduce blood lactate levels.(16)
  4. Increased concentrations of heat shock proteins (HSPs): HSPs and variations in the HSP70 gene can reduce protein degradation and promote muscle growth. HSPs also provide longevity and anti-aging benefits. (36,37,38,39) A growing body of literature supports the role of heat shock proteins in heat adaptation which allows organisms to perform work in high-temperature environments.(24)
  5. Increased prolactin release: Prolactin is a hormone produced in the pituitary gland. Named originally after its function to promote milk production (lactation) in mammals, it has since been shown to have more than 300 functions (reproductive, metabolic, fluid regulation, regulation of the immune system and behavior). Prolactin is an indirect marker of central fatigue.(49) A study comparing the prolactin responses of subjects reaching exhaustion via cycling to subjects heated to the same core temperature passively found that with both forms of heating the prolactin response was the same. The conclusion is that core temperature is the key stimulus for prolactin release.(20)
  6. Reduced insulin resistance. Hyperthermic conditioning has been shown to protect skeletal muscle from high-fat diet–induced insulin resistance and provide strong evidence that HSP induction in skeletal muscle could be a potential therapeutic treatment for obesity-induced insulin resistance.(50)

IV.BENEFITS FOR THE BRAIN

  1. Increased levels of prolactin: Prolactin is important for the promotion of myelin growth (which helps the brain function faster and repair nerve cell damage).(49) Studies have compared the prolactin responses of subjects reaching exhaustion via cycling to subjects heated to the same core temperature passively. It was found that with both forms of heating the prolactin response was the same. The conclusion is that core temperature is the key stimulus for prolactin release.(20)
  2. Increased endorphin levels: Brain chemicals known as neurotransmitters include “endorphins”, which function to transmit electrical signals within the nervous system. At least 20 types of endorphins have been demonstrated in humans. Endorphins can be found in the pituituitary gland and in other parts of the brain, or distributed throughout the nervous system.(122) Stress and discomfort (pain) are the two most common factors leading to the release of endorphins. Endorphins interact with the opiate receptors in the brain to reduce perception of pain (and act similarly to drugs such as morphine and codeine). In addition to decreased feelings of pain, secretion of endorphins leads to feelings of euphoria, modulation of appetite, release of sex hormones, and enhancement of the immune response.(122) The so-called “runner’s high” can result from a boost in endorphin levels, and the sense of well-being associated with intensive endurance athletics. Thermal conditioning and ATE also boost endorphin levels.(49) The boost in endorphin levels associated with running is believed to be related to heat stress. Animal studies have found that heat stress from thermal exposure can significantly increase endorphin levels.(22)
  3. Increased heat shock protein* (HSP) production: When injury occurs to a part of the brain, such as stroke or traumatic injury, HSP production is often increased to repair damage (95)
  4. Increased brain-derived neurotrophic factor* (BDNF): Research has established that exercise triggers the production of BDNF, which helps support the growth (and survival) of existing brain cells and the development of new ones (certain types of exercise have been shown to triple the synthesis of BDNF in the human brain)!(98). BDNF is a protein or “neuropeptide”- a member of the neurotrophin family of growth factors—known to be important for long-term memory.(99) As humans age, BDNF levels typically fall. This decline is one of the main reasons brain function generally deteriorates in the elderly. Research has shown that exercise can help to counteract these age-related drops in BDNF and can restore young levels of BDNF in the aging brain. BDNF activates brain stem cells to produce new neurons and triggers other important chemicals. Increased neurogenesis is believed to enhance learning, long-term memory and cognitive function as well as ameliorate anxiety, depression, schizophrenia, epilepsy, Alzheimer’s disease, drug addiction, obesity and other conditions.(46) A recent study with 15 subjects showed increased levels of serum BDNF from baseline of 13% and 30% with cycle ergometer exercise.(86) Another study with 11 subjects showed increased levels of serum BDNF which were enhanced with exercise in the heat. It was shown that heat stress increased the expression of BDNF more than exercise alone.(47) Since permeability of the blood–brain barrier increases with exercise in the heat, the opinion of the researchers was that thermal exercise causes a higher cerebral output of BDNF.(47)
  5. Increases perfusion and size of hippocampus: The hippopcampus generally shrinks in late adulthood, resulting in impaired memory and increased risk of dementia. A study with 120 older adults without dementia showed that exercise intervention increases cerebral blood volume and perfusion and the size of hippocampus.(87)
  6. Improves cognitive processes and memory: Increased cerebral blood flow and oxygenation, in addition to increased levels of serum BDNF as shown above, can improve cognitive processes and memory.(65) Studies have shown that both hyperthermic conditioning (65) and exercise improve cognition and brain performance, including memory.(85, 86, 87)
  7. Increases production of norepinephrine: Studies have shown that active thermal exercise and hyperthermic conditioning increase norepinephrine by as much as 310% (11,12) and 86% (48). Norepinephrine helps improve focus and attention to detail.(97)BENEFITS FOR THE MUSCLES

Our muscles are continually waging a war between the growth of new muscle cells (protein synthesis) and degradation of our existing proteins. The key factor is our net protein synthesis which takes into account both new protein synthesis and degradation. ATE reduces the amount of protein degradation taking place and therefore boosts net protein synthesis as follows:

A.ATE creates increased muscle mass:

1.Increased heat shock proteins* (HSPs): Heat acclimation increases net protein synthesis and muscle growth.(14,15) Increased production of heat shock proteins (HSPs) promotes muscle growth and reduces protein degradation.(14,15) Protein degradation occurs naturally during both muscle use and disuse. HSPs induced by heat help to both prevent and repair damaged proteins. HSPs are used by the cells to counteract potentially harmful stimuli.(14,15) HSPs can prevent damage by scavenging free radicals and supporting cellular antioxidant capacities via their help in maintaining glutathione levels.(14,15)  HSPs also repair misfolded and damaged proteins so proper structure and function is maintained.(14,15)

  1. Increased muscle mitochondria*: Research has shown that both heat exposure and high intensity exercise cause heat shock and oxidative stress (generation of O2− and H2O2). In addition, both exercise and ATE training promote mitochondrial biogenesis (2–3-fold increases in muscle mitochondria). (23,24,25).

3.Increased levels of human growth hormone* (HGH): ATE increases muscle growth by large induction of HGH.(12,13,5)  Studies have shown that exercise in high heat (40 degrees C.) resulted in increased HGH concentrations from the resting value both in the first and last heat tests.(5) The studies also showed that resting aldosterone (HGH) concentration was increased after heat acclimation.(5) Another study showed that exercise in a heated (40 degrees C.) climatic chamber almost doubled plasma HGH from levels achieved with the same exercise done under thermo-neutral (23 degrees C.) conditions.(92) Studies have shown that the major anabolic effects of HGH in skeletal muscle may result from the inhibition of muscle protein degradation, which results in net increases in protein synthesis.(18) Another study concluded that the administration of HGH to athletes for four weeks decreased muscle protein oxidation and degradation by 50%.(28)

  1. Increased production of muscle proteins: Exercise in heat contributes to improved protein synthesis.(11,14,15), and heat acclimation increases net protein synthesis and muscle growth.(14,15) Stimulation of the uptake of amino acids into muscle cells increases protein synthesis.(55) An animal study utilizing intermittent hyperthermia induced significant HSP in skeletal muscle which augmented muscle growth by 30%.(14) The animal study also showed that increased HSP expression can persist for 48 hours after heat shock.(14,15)
  2. Reduced protein degradation and protection against degenerative muscle tissue conditions: Muscle growth can be promoted by triggering the release of heat shock proteins (HSPs) which reduce the amount of protein degradation that naturally occurs during both muscle use and disuse.(14,15) Human growth hormone (HGH) also decreases protein degradation. Reduced protein degradation increases the net protein synthesis in the muscles and therefore promotes muscle growth.(14,15) It has also been shown that exercise in heat increases concentrations of HSPs, which may illustrate a cellular adaptation of heat acclimation in humans.(23) HSPs also help repair damaged proteins and help maintain proper protein structure and function, and thereby help protect against degenerative muscle tissue conditions.(14,15)
  3. Reverses age-related muscle atrophy (sarcopenia): Sarcopenia [age-related loss of muscle] affects about 10 percent of those over 60, with higher rates as age advances. Causes of the loss of muscle mass or strength include hormonal changes, sedentary lifestyles, oxidative damage, infiltration of fat into muscles, inflammation and resistance to insulin.(49) Exercise in heat contributes to improved protein synthesis. (11,14,15) Exercise in heat increases concentrations of HSPs, which may illustrate a cellular adaptation of heat acclimation in humans. (23)
  4. Reduces levels of lactic acid in the blood: Increased levels of lactate in muscles causes fatigue during exercise. Reduced lactate production can increase the capacity for prolonged physical activity. It is believed that this is because of increased blood flow to the muscles.(29) Exercise performed in a hot environment has been shown to reduce blood lactate levels.(16)
  5. Reduced muscle glycogen use: The reduced usage of glycogen by the muscles results from increased blood flow to the muscles.(7,8) Studies show that exercising in hot environments reduces muscle glycogen use by 40 to 50% and show reduced rates of glycogen depletion due to improved muscle perfusion. (7,8). Additional studies show that heat acclimation leads to sparing of muscle glycogen associated with enhanced ability to perform highly intense exercise following prolonged exertion in the heat.(7)
  6. Increased lactate threshold: Increased levels of lactate in muscles causes fatigue during exercise. Reduced lactate production can increase the capacity for prolonged physical activity (it is believed this is because of increased blood flow to the muscles).(29) Exercise performed in a hot environment has been shown to reduce blood lactate levels.(16)
  7. Improved recovery from muscle injury: To return to a healthy condition after injury, muscle regrowth must occur. Muscle regrowth after immobilization occurs as a result of elevated heat shock protein levels. Brain-derived neurotrophic factor*(BDNF) is also secreted by muscle cells and plays an important role in muscle repair and growth.(30) Studies show that exercise increases serum BDNF.(86) This increase can be enhanced with exercise in the heat. Since permeability of the blood–brain barrier increases with exercise in the heat, it is believed that this causes a higher cerebral output of BDNF.(47) Exercise in heat increases concentrations of HSPs, which may illustrate a cellular adaptation of heat acclimation in humans. (23)
  8. Reduced neuro-motor degradation: Brain-derived neurotrophic factor (BDNF) also protects neuro-motors—the most critical elements in muscle– from degradation.(60) Studies show that exercise increases serum BDNF. (86) This increase can be enhanced with exercise in the heat. Since permeability of the blood–brain barrier increases with exercise in the heat, it is believed that this causes a higher cerebral output of BDNF.(47)
  9. Improved insulin sensitivity: Insulin is an endocrine hormone responsible for promoting the uptake of glucose into muscle and adipose tissue. Insulin is also important for protein metabolism and increasing protein synthesis by stimulating the uptake of amino acids into the muscle.(94). In overweight individuals, insulin levels are elevated because the tissues do not respond properly to insulin (“insulin insensitivity”). This condition impedes the ability of glucose to enter muscle cells, causes high blood sugar levels and increases in the amount of glucose entering fat cells.(10,29)  Studies have shown that ATE helps to reduce insulin resistance by improving insulin sensitivity and decreasing muscle protein catabolism. Animal studies have found that 30 minutes heat exposure three times per week for a period of 12 weeks can result in a 31 percent decrease in insulin levels.(10) Lower insulin levels help maintain higher sensitivity to insulin and promote the entry of glucose into muscle cells.(10,29) Exercise has been shown to significantly reduce the risk of developing insulin resistance by improving glucose tolerance and insulin action in individuals predisposed to develop type 2 diabetes.(50) IMPROVED BODY COMPOSITION
  1. Exercise has been shown in numerous studies to improve body composition through reduced adiposity and improved weight control.(75-78, 88) Increased lean mass causes increased calorie burning.(29) Muscles burn over 90% of the Calories humans consume.(29)
  2. Muscle has special enzymes that enable burning of large amounts of calories in short periods.(53)

C.Both exercise and heat exposure cause heat shock and oxidative stress (generation of O2− and H2O2).

D.Both exercise and ATE training promote mitochondrial biogenesis (2–3-fold increases in muscle mitochondria) which leads to increased lean body mass. (23,24,25)

E.Hyperthermic conditioning has been shown to triple the synthesis of BDNF in the human brain. (98) Studies have also shown that BDNF is important for thermogenesis (the ability of cells to burn fat to produce heat) and for controlling appetite and satiety.(110)

VII. GREATER LONGEVITY

  1. ATE and greater longevity: A recent study published in JAMA Internal Medicine showed that thermal treatments are associated with greater longevity. The study of over 2,000 middle-aged men in Finland found that fatal cardiovascular disease was 27% lower for men who used the sauna 2 to 3 times per week and 63% lower in men taking 4 to 7 sauna sessions each week!(63)
  2. Increased HSPs: HSPs and variations in the HSP70 gene can also help provide longevity and anti-aging benefits. In flies and worms, heat exposure has been shown to increase lifespans by as much as 15% (36,37,37.5, 38,39) A growing body of literature supports the role of HSPs in heat adaptation which allows organisms to perform work in high-temperature environments.(24) Other animal studies have shown that chronic exercise enhances HSP70 accumulation in skeletal muscle.(61) Exercise in heat has also been shown to increase concentrations of HSPs, which may illustrate a cellular adaptation of heat acclimation in humans. (23)
  3. Foxo3 Gene*: Another molecular pathway that may explain how heat exposure can improve longevity is a gene that is associated with longevity known as Foxo3*. Foxo3 is one of the four mammalian Foxo genes, and it is activated by heat stress. Humans with a polymorphism that makes more of this gene have up to a 2.7fold increased chance of living to the age of 100.(97) In mice, having more of their homologous version of this gene can extend their lifespan by up to 30%.(96) The mechanism by which Foxo3 increases longevity has to do with the fact that it is a master regulator of many different genes. When the Foxo3 gene is “on”, it increases the expression of a number of genes that increase resistance to many of stressors that occur with aging. Many of the genes that foxo3 increases typically decrease with age, so it is important for longevity to boost their expression.(97) One critically important stress that Foxo3 protects against is DNA damage. The same type of reactive byproducts (from normal metabolism and immune function) that damage proteins in the cell also damage DNA.(97) DNA damage often leads to mutations. Damaged cells with mutations often replicate to form cancer. Foxo3 increases the expression of DNA repair genes that help prevent cell mutations.(97) Foxo3 also increases the expression of genes that kill cell damaged cells so that they do not become cancer cells.(97) Foxo3 makes cells more resilient to damage by increasing the expression of genes that combat damage such as antioxidant genes which prevent the damage from reaching the cell. Finally, Foxo3 increases the expression of genes responsible for immune function (which generally declines with age). Boosting the immune system enables us to combat bacteria, viruses, and cancer cells more effectively which leads to longer and healthier lives.(97)

*Note: See appendix for additional information.

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APL (American Performance Labs) is a research group dedicated to the collection, analysis, and dissemination of published research and articles on the science of hyperthermia and the various applications, technologies and protocols for the use of hyperthermic conditioning.