Epigenetics: Strengthening the Immune System

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Part
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Epigenetics: Strengthening the Immune System

This report provides an overview of epigenetics. Part (A) covers the relationship between epigenetics and the immune system, highlighting its role in cellular memory and how it differs by gender and changes as we age. Part (B) suggests methods of boosting the immune system via epigenetics, including physical activity and healthier eating. Full details are provided below.

Part (A): This section provides insights on the link between epigenetics and the immune system.

Epigenetics Form the Basis of Molecular Cellular Memory

  • When a single gene has a chemical compound added to it and the compound regulates the gene's activity in some way, the gene has undergone an epigenetic change. The combination of these changes is referred to as the epigenome.
  • These chemical compounds do not modify the genetic sequence, but instead attach themselves to the top of the molecular strand.
  • When a cell divides through meiosis or mitosis, some epigenetic changes attached to its genetic sequence can be replicated as well.
  • In this way, epigenetic changes form the basis of generational cellular memory (meaning the changes that are passed on from a parent cell to its offspring), thus forming the evolving immune system response.
  • As an example, epigenetic mechanisms have been demonstrated to influence the regulation of T and B lymphocytes, both of which has a major role in the immune system.

Environmentally-influenced Epigenetic Modifications Can Weaken Immune System

  • Epigenetic changes can stem from either intrinsic (metabolic profile or hormones, for example) or extrinsic (diet, pollution, or stress, as examples) sources.
  • An individual's lifestyle is said to "significantly" affect the epigenome.
  • Eating less produces an epigenetic effect that reduces the metabolic rate and has been demonstrated to contribute to a 20 percent longer lifespan in mice.
  • Obesity in adolescents produces an epigenetic effect (DNA methylation) that alters blood cells and increases harmful oxidative exposure.
  • Changes to the environment of a parent can yield improvements to its offspring even if those changes don't manifest in the parent. For example, a parent mouse with the Agouti gene is susceptible to obesity, diabetes, and certain cancers. It is also yellow. When fed B vitamins, the parent does not recover; however, the offspring of these mice have a suppressed Agouti gene. This means they have no susceptibility to the health vulnerabilities of their parents, and they are brown rather than yellow.

Epigenetic Changes Vary with Age and Gender

  • Aging is associated with a declining immune system response as a result of epigenetic changes that affect the regulation of key disease-fighting agents such as T and B lymphocytes.
  • Aging causes oxidative stress, which in turn causes epigenetic effects. As an example, SIRT-1 (a histone deacetylate) decreases in protein level as an individual ages, causing an increase in the acetylation of lysine 16 of histone H4K16.
  • Age-related epigenetic changes resulting in declining T cells and increasing monocyte and cytotoxic cell functions happen at a greater magnitude in males.
  • For both men and women, age-related epigenomic changes experience an initial spike around the late-30s.
  • A second spike of age-related epigenomic changes occurs earlier and stronger in men.
  • Epigenomic differences accelerate after age 65, leaving males with higher innate and pro-inflammatory activity and lower adaptive activity.
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Part (B): This section provides insights on methods of combating viruses and diseases from an epigenetic standpoint.

Foods to Avoid

  • Epigenetic changes caused by the Western diet may not all be reversible even when a healthier diet is adopted. Eating a cereal-based diet for 4 weeks improved the acute inflammation response in mice after eating a heavy Western diet; however, many of the changes to the immune system were not reversed.
  • Food that is high in calories contributes to negative epigenetic changes in the immune system and should be avoided. High calorie food is treated like a bacterial infection by the immune system, causing an overactive response.
  • Food that is high in fat contributes to negative epigenetic changes in the immune system and should be avoided. High fat food is also treated like a bacterial infection by the immune system, causing an overactive response.
  • Food that is low in fiber contributes to negative epigenetic changes in the immune system and should be avoided.
  • Fast food contributes to negative epigenetic changes in the immune system and should be avoided.

Foods to Eat

  • Eating foods high in zinc such as meats and shellfish improves the immune system's response to inflammation and thus improves health outcomes for cancer, diabetes, and other diseases. For adults, 8-11 mg of zinc should be consumed each day.
  • Fruit has a different effect on the immune system than juice. Fruit improves macrophage modulation while juice improves B and T cell modulation. This suggests both fruit and juice are important for immune system health.
  • Foods that are high in vitamin A are recommended as vitamin A has a proven role in affecting the innate and the adaptive immune system. The recommended dietary allowance for men is 900mcg. For women, it is 700mcg.
  • High vitamin A foods include liver, king mackerel, salmon, bluefin tuna, goat cheese, hard-boiled eggs, and cream cheese.
  • A vegetarian diet contributes to an improved immune system due to the regular consumption of lower-fat, higher-vitamin foods. Plant-based diets tend to be higher in fiber, which improves immune system response.
  • Probiotic-heavy foods such as yogurt and kefir improve the immune system response and limit the effects of various inflammatory disorders through epigenetic mechanisms.

Exercise

All forms of physical activity appear to have an effect on the immune system.
  • Physical activity plays a critical role in influencing epigenetic changes that improve the reaction of the immune system.
  • Physical activity delays the onset of aging. Aging contributes to immune system decay through epigenetic mechanisms.
  • The effect of physical activity on improving particular conditions (such as hypertension) is based on the genetic predisposition of the individual patient. As such, personalized exercise prescriptions are the best method of improvement.
  • Increased physical activity leads to decreased levels of lymphocytes in circulation, thus decreasing the inflammation response of the immune system. This is particularly beneficial for immune system disorders caused by an overreaction of the inflammatory response.
  • Women that performed an incremental step test (beginning with a 3-minute warm up at 50 watts power output, and then increasing in power at increments of 25 watts every 2 minutes until exhaustion) had an increase in natural killer cells while exercising and then experienced a drop in natural killer cells for up to 48 hours afterwards. Natural killer cells play a role in overactive immune system responses (including arthritis and diabetes), meaning that having less can be favorable.
  • Resistance-based exercises cause epigenetic changes that lead to healthy skeletal muscle by improving energy metabolism and insulin sensitivity. Endurance-based exercises caused additional metabolic alterations. Both resistance- and endurance-based exercises are recommended to thwart diseases.
  • Low-intensity exercises (such as tai chi) undertaken by women for at least 3 years has shown epigenetic improvements in immune system changes associated with aging.


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Quotes
  • "Epigenetic factors, such as DNA or histone modifications, are indispensable for precise gene expression in diverse immune cell types. Thus a disruption of epigenetic landscapes likely has a large impact on immune homeostasis."
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  • "Epigenetic changes, such as DNA methylation, histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by regulating gene expression."
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  • "DNA modifications that do not change the DNA sequence can affect gene activity. Chemical compounds that are added to single genes can regulate their activity; these modifications are known as epigenetic changes."
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  • "Furthermore, environmental factors that are known to exert disease promoting or protecting effects mediate their effects through changes in the epigenome in various inflammatory diseases."
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  • "Epigenetic mechanisms include DNA methylation and chromatic remodelling and they provide a molecular basis for cellular memory."
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  • "DNA methylation is a stable epigenetic mark that can be inherited through multiple cell divisions. "
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  • "Consistent evidence has showed the regulation of innate immune cells, and T and B lymphocytes by epigenetic mechanisms."
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  • "Histone deacetylates, such as SIRT-1, have been shown to decrease in protein level during physiological aging, leading to age-related increase in the acetylation of lysine 16 of histone H4 (H4K16)."
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  • "These changes are greater in magnitude in men and accompanied by a male-specific decline in B-cell specific loci. "
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  • "By feeding them B vitamins, he did not “cure” these genetically ill mice, but the beneficial effect was felt on the offspring [6]."
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  • "PA can reverse at least some of the unwanted effects of a sedentary lifestyle, contributing to the treatment of pathologies such as hypertension and diabetes, to the delay of aging and neurodegeneration, and even to the improvement of immunity and cognitive processes. "
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  • "Since immunohistochemically antibody-based assessment of DNA-methylation is relatively vague, and TDBS does not allow the analysis of a wide range of genes, this pilot-study aims to generate first insights into the influence of a single bout of exercise on gene specific DNA-methylation using a microarray approach in isolated NK-cells and open the field for such analyses."
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  • "Numerous studies suggested the involvement of NK cells in pathogenesis of such a common autoimmune diseases as juvenile rheumatoid arthritis, type I diabetes and autoimmune thyroid diseases. "
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  • "Resistance exercise in humans induced epigenetic changes in pathways associated with energy metabolism and insulin sensitivity, contributing to healthy skeletal muscle. Endurance exercise also caused modifications in biomarkers associated to metabolic alterations through changes in DNA methylation and the expression of specific miRNAs. However, both resistance and endurance exercise are necessary to obtain a better physiological adaptation and a combination of both seems to be needed to properly tackle the increasing prevalence of non-communicable pathologies."
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  • "The long-term changes may contribute to type 2 diabetes, arteriosclerosis, and several other conditions wherein inflammation is thought to play a part, and which have been linked to consumption of a Western diet."
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  • "Even long after switching to a healthy diet, inflammation towards innate immune stimulation is more pronounced. These changes may be involved in the development of arteriosclerosis and diabetes."
Quotes
  • "Not getting enough of this important mineral could lead to chronic disease involved in inflammation such as cancer, diabetes, and cardiovascular disease. "
Quotes
  • "These data suggest a role for epigenetic regulation in fruit and juice-specific health benefits and demonstrate independent associations with distinct immune functions and cell types, suggesting that these groups may not confer the same health benefits. Identification of such differences between foods is the first step toward personalized nutrition and ultimately the improvement of human health and longevity."
Quotes
  • "Vitamin A has an important role in the immune system, influencing both the innate and the adaptive immune systems [2]. In innate immunity, retinoic acid mainly inhibits cytokine production of monocytes, macrophages, and dendritic cells and regulates cell differentiation [2–4]."
Quotes
  • "Vitamin A is a fat-soluble vitamin that plays an essential role in maintaining vision, body growth, immune function and reproductive health."
Quotes
  • "Eating a low-fat, plant-based diet may help give the immune system a boost. The immune system relies on white blood cells that produce antibodies to combat bacteria, viruses, and other invaders. Vegetarians have been shown to have more effective white blood cells when compared to nonvegetarians, due to a high intake of vitamins and low intake of fat."
Quotes
  • "Over the past 40 years, probiotics have been shown to impact the immune system, both in vivo and in vitro."