While epigenetic modifications
can be modified by lifestyle,
they are complex systems.
- Epigenetics refers to the way your behaviors and environment can cause changes that affect the way your genes work.
- Epigenetics turns genes "on" and "off."
- Your epigenetics change as you age, both as part of normal development and aging and because of exposure to environmental factors that happen over the course of your life.
- Epigenetic changes can affect your health in different ways.
- Epigenetics change as you age as part of normal development.
- Certain diseases can change your epigenetics. In addition, some epigenetic changes can make you more likely to develop certain diseases, such as cancer.
- Epigenetics can change in response to your behaviors and environment.
There are various epigenetic influences on humans by different sources present in the environment. While some of these might be beneficial for health and behavior, others might be harmful and interfere with the body and mind creating an imbalance, which might manifest as a disease or psychological disorder.
Some of the beneficial influences listed are exercise, microbiome (beneficial intestinal bacteria), and alternative medicine whereas harmful influences include exposure to toxic chemicals and drugs of abuse.
Factors such as diet, seasonal changes, financial status, psychological state, social interactions, therapeutic drugs, and disease exposure might have beneficial or harmful effects depending on the specific nature of the influence.
The environment thus complements and shapes human health. With the help of extended research in the field, we might be able to steer these influences in a positive way.
Enzymatic activity in response to the environment promotes addition or removal of epigenetic tags on DNA and/or chromatin, sparking a cavalcade of changes that affect cellular memory transiently, permanently or with a heritable alteration.
The literal meaning of the term epigenetic is “on top of or in addition to genetics.” The series of chemical tags that modify DNA and its associated structures constitute the epigenome, and include any genetic expression modifier independent of the DNA sequence of a gene.
The genome defines the complete set of genetic information contained in the DNA, residing within the cells of each organism.The epigenome, on the other hand, comprises the complex modifications associated with genomic DNA, imparting a unique cellular and developmental identity.
The epigenome integrates the information encoded in the genome with all the molecular and chemical cues of cellular, extracellular, and environmental origin. Along with the genome, the epigenome instructs the unique gene expression program of each cell type to define its functional identity during development or disease (Rivera and Ren, 2013).
The epigenome also, in some sense, represents the ability of an organism to adapt and evolve through expression of a set of characteristics or phenotypes developed in response to environmental stimuli.
Thus, in contrast to the consistency of the genome, the epigenome is characterized by a dynamic and flexible response to intra- and extra-cellular stimuli, through cell-cell contact, by neighboring cells, by physiology, or entirely by the environment that the organism is exposed. Cytokines, growth factors, alterations in hormonal levels as well as release of stress-response and neurotropic factors are some examples of molecules that are modulated by the environment and which come under the category of epigenome modifiers. Ultimately, the environment presents these various factors to the individual that influence the epigenome, and the unique epigenetic and genetic profile of each individual also modulates the specific response to these factors
Your genes play an important role in your health, but so do your behaviors and environment, such as what you eat and how physically active you are. Epigenetics refers to how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes (mutations), epigenetic changes are reversible and do not change the sequence of DNA bases, but they can change how your body reads a DNA sequence.
Every cell in the organism carries an identical genome, however, despite the stability of these instructions, the terminal phenotype within an organism is not fixed and deviation is caused by gene expression changes in response to environmental cues.
DNA methylation, histone modification and RNA-associated silencing are the major ways these changes are controlled.
The methylome is the genomic distribution of methylated DNA sequence present in a cell and is capable of undergoing modification with respect to the environment or the developmental stage.
How do cellular biochemical changes cause epigenetic changes?
The effects of an epigenetic factor can be manifested as a global change in DNA methylation affecting multiple genes, or modified expression of very specific genes. The mechanisms and cellular pathways that are involved in the creation of these global or specific epigenetic changes are currently obscure.
For most genes, total reprogramming is necessary very soon after conception in order to start with an epigenetic “clean slate,” which then allows all of the specialized cells derived from the egg and sperm to develop with stable cell-specific gene expression profiles and remain properly differentiated. This happens in the fertilized egg: global DNA demethylation is followed by remethylation to reprogram the maternal and paternal genomes for efficient gene expression regulation. As a fertilized egg develops into a human baby, signals received cause steady changes in gene expression patterns. Epigenetic tags physically record the cell's experiences on the DNA, and stabilize gene expression. Each signal activates some genes, and inactivates others, as the cell develops toward its final fate. Early in development, most signals come from within cells or from neighboring cells. Different experiences cause the epigenetic profiles of each cell type to grow increasingly different over time. Eventually, hundreds of cell types form, each with a distinct identity and specialized function. Specifc genes are turned on and off at certain time intervals, and any disruption of this finely-tuned DNA methylation regulation may persistently alter gene expression. The fetal epigenome is most susceptible during this developmental period to epigenetic modifiers in the maternal environment. An error during such a crucial time might lead to an abnormal phenotypic outcome in the offspring.
Gene expression refers to the process of making proteins using the instructions from genes. A person's DNA includes many genes. Each gene includes instructions for making proteins. Additionally, there are other sections of DNA that are not part of any gene but are important for making sure the genes work properly. These DNA sections provide directions about where in the body the protein is made, when it is made, and how much is made.
While changes to the genes (mutations) can change the protein that is made, epigenetic changes affect gene expression to turn genes "on" and "off." This can mean that genes make proteins in cells and tissues where or when they normally would not, or that genes don't make proteins where and when they normally would. It can also mean that genes make more or less of a protein than they normally would.
There are several ways an environmental factor can cause an epigenetic change to occur. One of the most common ways is by causing changes to DNA methylation.
DNA methylation works by adding a chemical (known as a methyl group) to DNA. This chemical can also be removed from the DNA through a process called demethylation. Typically, methylation turns genes off and demethylation turns genes on. Thus, environmental factors can impact the amount of protein a cell makes. Less protein might be made if an environmental factor causes an increase in DNA methylation, and more protein might be made if a factor causes an increase in demethylation.
Maternal health can predict childhood development, health outcome and disease consequences. More specifically, fetal programming describes how the in utero environment impacts molecular development in the fetus via epigenetic remodeling.
Environmentally induced epigenetic variation is also driven by paternal factors, and they are as important as their maternal counterparts in influencing epigenetic outcome in offspring.DNA methylation in sperm can be influenced by paternal alcohol consumption, and paternal exposure to toxic chemicals
Epigenetic influences continue to shape an individual after birth. Even at birth, the type of delivery seems to have an effect on the offspring being born. For example, offspring born from ceasarian section have shown to have global hypermethylation in leucocytes as compared to those born vaginally
After birth and as life continues, infancy and childhood, a wider variety of environmental factors begin to play a role. As in early development, signals from within the body continue to be important for many processes, including physical growth and learning, but gradually more and more external environmental and social influences begin to take effect.
Early life positive and negative experiences like maternal care, stress adaptation, and early life adversities contribute to a biological memory, and epigenetic modifications of DNA are responsible for imprinting such influences in to the neuronal circuits of the developing brain which can have life-long impacts.
During infancy and childhood maternal care and social environment shape a child's psychology.
Maternal bonding has a profound effect on the physical and psychological welfare of children. Epigenetic mechanisms interact with and impact the hypothalamic-pituitary-adrenal axis of the stress response in the brain.
Poverty and neglect have direct negative impacts upon future development.
The quality of family life including maternal care continues to influence the physiology and psychology of the child such that persistent neglect, emotional or sexual abuse hamper growth and intellectual development and increase risk of disorders like obesity during adulthood.
The transition from childhood to adolescence is accompanied by temperamental and behavioral changes including emergence of sexual behavior which is driven by underlying hormonal changes that can also be influenced by environmental factors. Puberty is a primary event of adolescence and is itself a major development event of human life.
Puberty involves the maturation of certain regions of the pre-frontal cortex in the brain, and it has been suggested that environmental influences like stress can trigger neuropsychiatric diseases via epigenetic mechanisms during such vulnerable plastic development.
Adulthood, various external epigenetic factors modulate the biology of an individual at a physical and emotional level. Some of the most important exogenous factors influencing human health are described hereafter.
Generally, during the aging process, global hypomethylation of DNA occurs in a repetitive sequence pattern that may promote genomic instability. Not only is aging correlated with hypomethylation of proto-oncogenes, but also with hypermethylation of tumor suppressor genes, potentially leading to increased risk of cancer and other diseases.
Epigenetics and development
Epigenetic changes begin before you are born.
All your cells have the same genes but look and act differently. As you grow and develop, epigenetics helps determine which function a cell will have—for example, whether it will become a heart cell, nerve cell, muscle cell, or skin cell.
EXAMPLE: Nerve cell and muscle cell. Your nerve cells and muscle cells have the same DNA, but they work differently. A nerve cell transports information to other cells in your body. A muscle cell has a structure that aids in your body's ability to move. Epigenetics allows the muscle cell to turn on genes to make proteins important for its job and turn off genes important for a nerve cell's job.
Epigenetics and age
Your epigenetics change throughout your life. Your epigenetics at birth are not the same as your epigenetics during childhood or adulthood.
EXAMPLE: A newborn, 26-year-old, and 103-year-old. Scientists measured DNA methylation at millions of sites in a newborn, 26-year-old, and 103-year-old. The level of DNA methylation decreased with age. The newborn had the highest level of DNA methylation, the 103-year-old had the lowest level of DNA methylation, and the 26-year-old had a DNA methylation level that was between that of the newborn and the 103-year-old.1
Epigenetics and exposures
Your epigenetics can change in response to your behaviors and environment.
Nutrition during pregnancy
A pregnant woman's environment and behavior during pregnancy, such as whether they eat healthy food, can change the baby's epigenetics. Some of these changes can remain for decades and might make the child more likely to get certain diseases.
EXAMPLE: Dutch Hunger Winter famine (1944–1945). People whose mothers were pregnant with them during the famine were more likely to develop certain diseases, such as heart disease, schizophrenia, and type 2 diabetes.2 Around 60 years after the famine, researchers looked at DNA methylation levels in people whose mothers were pregnant with them during the famine. These people had increased DNA methylation at some genes and decreased DNA methylation at other genes, compared with their siblings who were not exposed to famine before birth. 345These differences in DNA methylation could help explain why these people had an increased likelihood for certain diseases later in life.
Certain mutations make you more likely to develop cancer. Likewise, some epigenetic changes increase your cancer risk. For example, having a mutation in the BRCA1 gene that prevents it from working properly makes you more likely to get breast and other cancers. Similarly, increased DNA methylation that results in decreased BRCA1 gene expression raises your risk for breast and other cancers.10 While cancer cells have increased DNA methylation at certain genes, overall DNA methylation levels are lower in cancer cells compared with normal cells.
Different types of cancer that seem similar can have different DNA methylation patterns. Epigenetics can be used to help determine which type of cancer a person has or can help to find hard-to-detect cancers earlier. Epigenetics alone cannot diagnose cancer. Cancers would need to be confirmed with further screening tests.
EXAMPLE: Colorectal cancer. Colorectal cancers have abnormal DNA methylation near certain genes, which affects expression of these genes. Some commercial colorectal cancer screening tests (for example, Cologuard®) use stool samples to look for this abnormal DNA methylation. It is important to know that if you have one of these tests and the result is positive or abnormal, you will need to have a colonoscopy, which is a procedure to check your colon for cancer.
Epigenetics across the human lifespan
Epigenetics has the potential to explain various biological phenomena that have heretofore defied complete explication. This review describes the various types of endogenous human developmental milestones such as birth, puberty, and menopause, as well as the diverse exogenous environmental factors that influence human health, in a chronological epigenetic context. We describe the entire course of human life from periconception to death and chronologically note all of the potential internal timepoints and external factors that influence the human epigenome.
Ultimately, the environment presents these various factors to the individual that influence the epigenome, and the unique epigenetic and genetic profile of each individual also modulates the specific response to these factors.
During the course of human life, we are exposed to an environment that abounds with a potent and dynamic milieu capable of triggering chemical changes that activate or silence genes. There is constant interaction between the external and internal environments that is required for normal development and health maintenance as well as for influencing disease load and resistance.
For example, exposure to pharmaceutical and toxic chemicals, diet, stress, exercise, and other environmental factors are capable of eliciting positive or negative epigenetic modifications with lasting effects on development, metabolism and health. These can impact the body so profoundly as to permanently alter the epigenetic profile of an individual. These diverse environmental factors cause both direct and indirect epigenetic changes and this knowledge can ultimately be used to improve personalized medicine.
The future of epigenetics holds tremendous promise for understanding the complexities involved in genetic regulation, cellular differentiation, aging and disease; and a more complete and comprehensive understanding of the mechanisms that underlie the formation and erasure of epigenetic marks could allow us to commandeer the process and possibly fine tune the human epigenome.
Ultimately, continued efforts to determine how and when epigenetic switches regulate gene function will elucidate the interplay between the genome, the epigenome, and the environment and facilitate the development and optimization of novel therapeutic tools.
In terms of future application, full understanding of these mechanisms will ultimately revolutionize personalized medicine.
Resources
- Learn. Genetics: Genetic Science Learning Center at the University of Utah provides a detailed explanation and interactive tutorial about epigenetics.
- National Human Genomic Research Institute: Epigenomics Fact Sheet provides answers to questions about the epigenome.
- National Institute of Environmental Health Sciences: Epigenetics provides information about epigenetics, epigenetic research, and a video about epigenetics.
- National Library of Medicine
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