What are Heat Shock Proteins (HSPs)?

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Also called “stress proteins”, HSPs or heat shock proteins are highly conserved proteins, which exist in the cells of all living beings, right from bacteria to humans. As a cell goes through a stressful condition such as extreme cold, heat, UV light exposure, oxygen deprivation or healing wounds, HSPs are produced.

Even under normal conditions, HSPs exist in cells and act as chaperones. HSPs play an important role in several cellular processes in your body, including cell signaling, immune function and regulation of the cell cycle. They regulate the proteins of the cells and ensure that they’re in the proper shape, proper place and at the proper time. For instance, HSPs aid new or damaged proteins to fold into the right shape that is vital for them to function.

HSPs also transport the proteins from a section of the cell to another and also transport the old proteins for disposal. HSPs also play an important role in presenting the peptides (or pieces of protein) on the surface of the cell, which helps the immune system to recognize the diseased cells.

The cells maintain a basal or constant level of HSPs under normal conditions that aid in the various aspects of protein synthesis such as folding, assembly, regulation, turnover and export. However, the normal immune function and metabolic processes of the body create reactive byproducts like reactive oxygen and nitrogen species, which can damage the proteins and also destroy their structure.

When they experience extreme changes in the environment, cells become stressed and the cellular proteins become damaged or unfold. This impairs their normal functioning and can increase their vulnerability to change even more. When exposed to stress caused by extreme temperatures, hypoxia (reduced oxygen levels) or decrease in the nutrient levels (fasting), the cells increase the production of HSPs in order to stabilize the proteins that have unfolded and repair/resynthesize the damaged proteins. This is called “heat shock response”, which occurs to protect the cell from being damaged.

The disordered proteins are the common features in proteins that are damaged and dysfunctional and they can clump or aggregate together, causing neurodegenerative diseases such as Parkinson’s disease, Huntington’s disease and Alzheimer’s disease and cardiovascular diseases. HSPs help to prevent protein aggregation and disorder by repairing the damaged proteins and studies reveal that HSPs may also help to protect against neurodegenerative diseases.

Heat shock response was first studied in 1962 in the fruit fly (Drosophila), by Ferruccio Ritossa, an Italian scientist. He discovered that in response to heat shock, the synthesis of these proteins increased, which he called heat shock proteins or HSPs.

On basis of their molecular structure, weight and function, HSPs are categorized into 5 major families i.e. HSP60, 70, 90, 100 and the a-crystallins or small HSP (sHSP). HSPs or chaperones play a major role in the processes listed below:

  • Folding and unfolding of proteins
  • Signaling and controlling the cell cycle
  • Assembly of the multiprotein complexes
  • Protecting the cells against stress

How Can You Benefit from HSPs?

In recent years, HSPs have been used as therapeutic agents in human, as well as veterinary medicine. HSP90 has shown immense potential in cancer diagnosis and treatment. Also, HSP60, HSP70 and small HSPs have shown promise in managing neurodegenerative diseases, autoimmune diseases, ischemia and cell death.

Studies show that HSP70, HSP27 and small HSPs can protect the neurons from several conditions. And the overexpression of HSP70 can help to delay the progression of Alzheimer’s disease and Parkinson’s. So, HSP70 can be a good option for the treatment of neurodegenerative diseases. Also, it is seen that there is a significant role played by HSP90 proteins in the development, survival and spread of different kinds of cancer and when HSP90 is inhibited, anti-cancer effects have been seen.

The role of HSPs is seen in physical and mental performance and both these improve when the body’s core temperature increases in small bursts. You can increase your stress tolerating ability, endurance and gain muscle mass easily by increasing the core body temperature. When you exercise strenuously, you feel that you’re overheating, which causes fatigue and exhaustion.

Studies show that when you experience this level of heat without working out, your body begins to adapt and reduces the overheating even when you work out. This is essentially because the cardiovascular system and thermoregulatory mechanisms of your body start adapting over time. The body then becomes capable of regulating its own core temperature via adaptation.

How Do Our Bodies Adapt?

Our bodies adapt in various ways such as:

  • By lowering the heart rate, making it more efficient.
  • Allowing more efficient transportation of oxygen to our muscles.
  • Increasing the RBC count.
  • Lowering the temperature of the body during workouts.
  • Increasing our sweat and sweat sensitivity by raising the thermoregulatory control.
  • Increasing the plasma volume, thereby optimizing the blood flow.
  • Increasing the blood flow to the tissues.

Sauna Therapy and HSPs

Sauna therapy is shown to elicit molecular mechanisms in the body in response to heat stress. The effects of heat stress are enabled by molecular mechanisms that reduce protein aggregation and damage and also activate the endogenous repair, degradation and antioxidant processes. Several of these responses are also generated when you exercise, following a moderate to vigorous intensity routine, which results in the production of heat shock proteins (HSPs), pro-inflammatory and anti-inflammatory factors and transcriptional regulators.

Studies revealed that undergoing a 30-minute sauna therapy session two times a week after exercising at the gym allowed the participants to run until they were completely exhausted by around 32% as compared to the baseline. This was accompanied by an increase of 3.5% in the RBC (red blood cells) count and an increase in the level of blood plasma by around 7.1%. The increase in the red blood cells essentially means that your muscles are getting more oxygen. And the increase in the RBCs compensates for a rise in the plasma level.

The heat shock proteins also affect our muscle cells. Both exercise, as well as heat, cause muscular hypertrophy that in turn, increases the size of the muscle cells and hence, your strength. Whether the muscle cells become bigger or get smaller depends on whether there is protein synthesis or degradation.

Heat acclimation helps in increasing protein synthesis and muscle hypertrophy while reducing degradation. Basically, heat conditioning works in 3 ways i.e.

  • Helping to induce heat shock proteins
  • Inducing growth hormone
  • Improving sensitivity to insulin

When you exercise, the energy needs of the muscle cells are increased. The mitochondria, i.e. the powerhouse of the cell, get active and begin to create energy via ATPs by making use of oxygen. However, this process also creates oxygen-free radicals, which cause protein degradation that limit the muscle gains that you have made by working out.

The HSPs allow a reduction in the oxygen-free radicals while retaining the protein synthesis from the workout. Exposure to heat produces a protective hormone response that targets the free radicals and repairs the damaged and misfolded proteins. In technical terms, this activates the mTOR pathway and boosts protein synthesis, while deactivating the FOXO pathway, reducing protein degradation.

It is seen that sauna therapy is a great method to increase the production of the human growth hormone because it is released naturally via sauna sessions. It has been demonstrated that two sessions of sauna therapy for 20 minutes at a temperature of more than 80ºC along with cooling results in a two-fold rise in the human growth hormone. While two 15-minute sauna therapy sessions at 100ºC, accompanied by a short cooling period in between the sessions, showed a five-fold increase in the human growth hormone.

In particular, heat stress activates the heat shock response. For instance, when healthy women and men sat for around 30 minutes in a heat stress chamber that was set at 163ºF, their HSP72 levels increased by around 49%. In another study, healthy women and men were exposed to deep tissue heat therapy for around 6 days and it was seen that there was an increase of the HSP90 and HSP70 levels of the participants by 38% and 45% respectively.

Also, there was an improvement in the participants’ mitochondrial biogenesis biomarkers and there was an increase in their mitochondrial function by around 28% as compared to the baseline levels. The activation of the HSPs is sustained for a long time, which suggests that heat acclimation is seen to induce whole body adaptations, which help to increase the body’s heat tolerance, which in turn, results in protective cellular adaptations.

In conclusion, we can see that sauna therapy offers several health benefits, ranging from improved endurance to mental and cardiovascular health to fertility. The heat stress that is produced through sauna use produces hermetic responses in the body that are catalyzed by molecular mechanisms, which help to protect the body from damage, akin to medium to rigorous exercise that can go a long way in preventing the effects of aging and improving overall health.


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