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Heat Shock Proteins & HSP70: How to Increase Them

Written by Joe Cohen, BS | Last updated:

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Heat shock proteins are created by cells. While they can help protect cells and prevent some diseases, heat shock proteins can also lead to artery problems or cancer. Read more below to find out about the benefits and drawbacks of heat shock proteins.

What Are Heat Shock Proteins?

Heat shock proteins (HSP’s) are a family of proteins which are created by cells during stressful situations.

These proteins can protect the cells from situations that would normally be lethal [1].

Health Benefits of Heat Shock Proteins

1) Heat Shock Proteins Act As Chaperones

HSPs are also molecular chaperone proteins. Chaperone proteins monitor and help regulate the folding of proteins. Protein folding is important for their specific roles. Proteins which do not fold appropriately can trigger an immune response and a host of other issues [1].

Having too many misfolded or unfolded proteins can lead to improper protein grouping/clumping and potentially resulting in different diseases like Huntington’s disease. Heat shock proteins help prevent the huntingtin protein from forming aggregates by binding to the protein and forming a coat over it [1].

2) HSPs Can Be Used In Huntington’s Disease Therapeutics

Huntington’s Disease is a disorder that affects nerve cells in the brain and can lead to mental decline and affects muscle movement.

A drug named geldanamycin is known to regulate a heat shock protein, Hsp90. Hsp90 can stimulate the production of Hsp70 in the cell, which relieves the toxicity in the cell.

When the production of heat shock proteins in the cell increase, they help reduce the toxicity in the cell from the mutant huntingtin protein [1].

3) HSPs Prevent Cell Death

When cells are stressed, a common response is to undergo cell death by one of two pathways, either necrosis or apoptosis. Heat-shock proteins are responsible for inhibiting both apoptotic and necrotic pathways [2].

4) HSPs Play A Role In Immune Response

When a cell is cancerous or infected by a pathogen, it creates proteins that are not normally found in the body. These proteins act as antigens, which are foreign substances that initiate an immune response. Immune cells, however, must be made aware of these antigens. Heat shock proteins, mainly Hsp70 or Hsp90, alert the immune cells to the antigens. They deliver the antigens to the immune system’s antigen-presenting cells (APCs) through surface receptors [3].

Heat shock proteins are the dominant antigens during infections and during the progression of certain autoimmune diseases [4].

Heat shock proteins inhibit inflammatory pathways [5].

Heat shock proteins make healthy cells stronger by protecting cells against stress and injuries, making you more resistant to diseases [4].

5) HSPs Make Sure Steroid Hormone Receptors Function

Hsp90 is mostly responsible for the function of the glucocorticoid receptor. When the receptor interacts with the heat shock proteins, expressions of the genes are increased [6].

Hsp90 is also responsible for the binding of estrogen, progesterone, androgen, and aldosterone [7].

6) HSPs Protect the Heart

Heat shock proteins can protect the heart. When they appear after mild stress in the heart, the heat shock proteins can protect against bigger stress [8].

HSPs can also help other heart defenses [9].

Hsp90 binds both endothelial nitric oxide synthase and soluble guanylate cyclase, which in turn are involved in vascular relaxation [10].

Hsp20 phosphorylation correlates well with smooth muscle relaxation and also serves a significant role in preventing platelet aggregation, cardiac muscle function and prevention of apoptosis after ischemic injury, and skeletal muscle function and muscle insulin response [11].

7) Heat Shock Proteins May Help Prevent Diabetes

Low levels of Hsp70 was shown to lead to higher insulin resistance in humans [12].

In rats, heat shock proteins interacted with insulin signaling. This lead to less insulin resistance and higher insulin sensitivity. Heat shock proteins may be used to prevent and treat diabetes in humans [13].

Negative Effects of Heat Shock Proteins

1) HSPs May Aid In Formation Of Atherosclerosis

Atherosclerosis (hardening of the arteries) is a disease where plaque builds up in your arteries. The plaque is made of fat, cholesterol, calcium and other substances in the blood. Over time the plaque hardens and as a result, narrows down your arteries. This greatly reduces the amount of oxygen-rich blood that can reach your organs and other parts of the body. This disease can lead to a heart attack, stroke, or even death. It can also affect the arteries of the heart and is called coronary heart disease [14].

HSPs are highly produced in the atherosclerotic lesions of humans. Risk factors for atherosclerosis including infection, oxidative stress, biomechanical stress (e.g. Shear stress on artery walls from blood), all lead to the overproduction of HSPs through the activation of heat shock transcription factor 1 [15].

2) Heat Shock Proteins Promote Cancer

Heat Shock Proteins that stop cell death may be involved in the formation of cancer [2].

Heat shock proteins are produced at high levels in cancer and provide an environment for tumor development leading to a poor prognosis and resistance to therapy (16).

HSP production can cause uncontrolled growth, reduced tumor suppression, enhanced cell survival and, metastatic (growth of malignant cells at a point away from the original cancer location) and angiogenic (formation of blood vessels from preexisting ones, essential for tumor growth) properties. Increased levels of Hsp90 help the formation of new treatment-resistant phenotypes by allowing new traits to develop in tumors. They can also interact with different cancer-causing genes to aid the progression of individual cancers (16).

HSPs promote uncontrolled cell growth while inhibiting death pathways (17).

HSPs also serve as biomarkers (a substance in organisms whose presence indicates a certain phenomenon) for the formation of cancer in some tissues and show the degree of progression and aggression of some cancers. Also, the increase of some HSPs can predict the response to certain anticancer treatments [18].

Genetics of Heat Shock Proteins

People vary in their natural ability to produce heat shock proteins.

Heat Shock Protein 70:

  1. RS1043618 (HSPA1L)
  2. RS2075799 (HSPA1L)
  3. RS2075800 (HSPA1L)
  4. RS2227956 (HSPA1L)

Ways that HSP Levels Decrease

Sleep Deprivation

Sleep deprivation can lead to a big decrease in heat shock protein levels [19].

Wine Phenolic Extracts Reduce HSP Levels

Total extracts of red wines decreased Hsp70 and Hsp27 levels and the numbers of a tumor and endothelial cells. These properties may be important in the potent anticarcinogenic (substance that inhibits the development of cancer) action of wine phenolics (a substance produced by plants to protect against plants) [20].

Ways that HSP Levels Increase

HSP numbers increase due to protein unfolding, misfolding or aggregation, as well as an increase in the production of non-native proteins in the body, whose function is to stabilize and refold proteins. Other reasons for an increase include oxidative stress, nutritional deficiencies, viral infection, some chemicals and exposure to cytokines, which are substances secreted by certain cells of the immune system that have a particular effect on cells [21].


Some of the conditions known to elicit the cellular stress reaction are similar to those experienced by cells in response to physical exercise. Hyperthermia, ischemia, oxidative, cytokine and muscular stress, glucose deprivation, and alterations in calcium and pH are potent inducers of HSP expression in different types of cells and tissues. Both exercise and calorie restriction are forms of mild stress that temporarily enhance HSP activity [22, 23].

Older patients who cannot exercise can also gain this increase in HSP since some of the effects of physical activity are caused by the temperature increase [24].

Life Stressors

  • Infection [25]
  • Inflammation [25]
  • UV [25]
  • Exposure of the cell to toxins (ethanol, arsenic, trace metals, among many others) [25]
  • Starvation [25]
  • Hypoxia (oxygen deprivation) [25]
  • Water deprivation [25]

Supplements to Increase HSP70

Mechanisms to increase HSP70:

“Whereas p300 has been shown to acetylate HSF1, deacetylation by the NAD+-dependent sirtuin (SIRT1) is involved in the attenuation phase of the heat-shock response by preventing HSF1 acetylation and DNA binding” [42].

Heat Shock Factor 1

HSF1 functions in the circadian clock as a circadian transcription factor.

HSF1 was shown to be highly rhythmic in its transcriptional activity.

Moreover, HSF1 enhanced the expression of Hsps at the onset of the active phase (human morning).

Hsf1-deficient mice have a longer free-running period and therefore more active than wild-type mice [45].

The cytokine interleukin 6 (IL-6) has been shown to derepress HSF1 by reducing the activity of GSKb [46].

Cells lacking HSF1 were susceptible to apoptotic cell death following exposure to heat stress [47]. In addition, mice lacking HSF1 also had elevated levels of tumor necrosis factor (TNF-), which resulted in increased mortality after endotoxin and inflammatory challenge [42].

In addition, mice lacking HSF1 also had elevated levels of tumor necrosis factor (TNF-), which resulted in increased mortality after endotoxin and inflammatory challenge [47].

SelfDecode can help you determine what your genes say about you – whether you’re a high or low heat shock protein producer.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thank you for your support.

About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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