EPIGENETICS
So, what is epigenetics? The main difference between genetics and epigenetics is that genetics studies the genes passed on from parent to child. All of the variations in the how the genes present themselves. Epigenetics is the study of how an inheritable trait can change the organism after modification and how the gene presents.
As the study of Genetics become more popular with crime shows and DNA research for personal background, almost everyone has some form of understanding of the power and importance of DNA. Now, there is a buzz about the study of Epigenetics and the amazing studies of how it can be used to rejuvenate and help us thrive for many years to come.
Epigenetics poses no new ethical concerns over the already established ethics governing genetics and DNA though it does encourage different framing common in the categories of scientific discovery.
Difference Between Genetics and Epigenetics | Definition, Fields, Role and Difference (pediaa.com)
The epigenetic is kind of like a sheet of paper wrapped around the DNA. It helps the transfer of the instructions into the cell and allows it to reproduce as intended. Sometimes the paper gets a crease in the paper causing some of the instructions to be distorted or completely skipped causing mutations, or in Epigenetics called epimutations.
What Causes Cancer
When epigenetic changes go wrong or miss a part of the instructions or recipe, cancer may develop. Two main groups of genes can be affected with cancer connections — oncogenes and tumor suppressor genes. Oncogenes can become overactive, and tumor suppressor genes may slow or go away.
“Your cells aren’t the only things that can trigger epigenetic changes, which are also known as epimutations. Things like smoking, not exercising enough, drugs, your diet, and environmental chemicals or radiation can result in chemical changes to DNA outside of genes that can result in cancer.”
How Epigenetics Impacts Cancer Treatment (webmd.com)
A common what to modify epigenome is to apply DNA methylation. That is to place a chemical group call methyl group to the building block of DNA. The methyl group consists of one carbon atom and three hydrogen atoms. when the groups are present, the gene will not produce any proteins. The gene is turned off.
Another common change is to modify histones. Histones are structural proteins in the nucleus of the cell. Adding or removing chemical groups like methyl groups or acetyl groups, which are made up of two carbon atoms, three hydrogen atoms and one oxygen atom, determine the shape of the chromosomes by how tightly it allows the DNA to wrap around the histone. The tighter it is wrapped around the histone, the less the gene will be able to be turned off.
Errors in the epigenetic process, such as modification of the wrong gene or failure to add a chemical group to a particular gene or histone, can lead to abnormal gene activity or inactivity. Altered gene activity, including that caused by epigenetic errors, is a common cause of genetic disorders. Conditions such as cancers, metabolic disorders, and degenerative disorders have been found to be related to epigenetic errors.
What is epigenetics?: MedlinePlus Genetics
Working Against Cancer
But what can we change? Where does cancer come from? When either the genome, the epigenome, or both undergo a mutation or a change that is not written in the instructions, it can cause cancer to form. The change can cause the epigenome to turn on or off a gene that controls the growth of a cell or the immune system response leading to uncontrolled cell growth, the first sign of cancer, or the inability of the immune system to react and destroy the tumors. By adding a methyl group to the DNA, certain types of cancers and be treated successfully. A drug, Temozolomide, is often used for this.
Changes can happen to the genome or epigenome by health or environment (disease, smoking, smog, etc.) These changes can also be brought about by aging.
Epigenomics Fact Sheet (genome.gov)
Epigenetic Therapies
“In general, there are two basic types of epigenetic therapies that are being tested for mesothelioma and other cancers by targeting specific proteins and enzymes in the body. These therapies have already shown success in treating lung cancer, breast cancer and lymphoma.”
Histone Deacetylase Inhibitors
- Histones are alkaline proteins that package and order DNA into nucleosomes, which allows for gene expression
- HDAC inhibitors modify histones to allow the DNA to be wrapped more tightly, which leads to the expression of genes associated with a healthy cell cycle and tumor suppression
DNA Methyltransferase Inhibitors
- Methyl is added to DNA (methylate) to impact the function of the genes and gene expression
- Research has shown the amount of DNA methylation significantly impacts survival (hypermethylation leads to shorter survival)
- DNMT inhibitors interfere with hyper methylation patterns, which can lead to tumor growth and development
Epigenetic Therapy | How it Works, Risks & Benefits (maacenter.org)
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Significant epigenetic changes occur through all stages of the aging process in all levels of chromatin and DNA organization.
“These include reduced global heterochromatin, nucleosome remodeling and loss, changes in histone marks, global DNA hypomethylation with CpG island hypermethylation, and the relocalization of chromatin modifying factors.” (Kane, AE, Sinclair, DA)
It is still under consideration as to why these changes occur, but the evidence is quickly growing that these epigenetic changes are affecting longevity and causing aging. New studies show that epigenetic changes that are related to age can be reversed with interventions such as cyclic expression of the Yamanaka reprogramming factors.
Yamanaka Factors
The factors are highly expressed in embryonic stem cells, and their over-expression can induce pluripotency in human somatic cells. These factors regulate the developmental signaling network necessary for embryonic stem cell pluripotency.
Yamanaka factors are often used to transform an adult cell into induced pluripotent stem cells; these have become important tools in Longevity research, but they are a double-edged sword, as over-exposure can lead to a cell’s identity being erased.
yamanaka factors — Search (bing.com)
This review presents a summary of epigenetic changes that occur in aging, highlights studies indicating that epigenetic changes may contribute to the aging process and outlines the current state of research into interventions to reprogram age-related epigenetic changes.
Epigenetic changes during aging and their reprogramming potential — PubMed (nih.gov)
Aging and Epigenetics
David Sinclair studies the effects of epigenome on the human body and how it reacts to aging. It is explained like a record or a CD. When the information is new, there are no playback problems. As the information ages, it develops scratches and playback issues. In Sinclair’s studies, they have been able to accelerate the “scratches” causing the aging process to accelerate. His theory is that if they can speed up the aging process, why shouldn’t they be able to slow it or even reverse it?
David A. Sinclair, A.O., Ph.D. is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. He worked as a postdoctoral researcher at M.I.T. with Dr. Leonard Guarente where he co discovered a cause of aging for yeast as well as the role of Sir2 in epigenetic changes driven by genome instability. In 1999 he was recruited to Harvard Medical School where he has been teaching aging biology and translational medicine for aging for the past 16 years. His research has been primarily focused on the sirtuins, protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction (CR) with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer. The Sinclair lab was the first one to identify a role for NAD+ biosynthesis in regulation of lifespan and first showed that sirtuins are involved in CR in mammals. They first identified small molecules that activate SIRT1 such as resveratrol and studied how they improve metabolic function using a combination of genetic, enzymological, biophysical and pharmacological approaches. They recently showed that natural and synthetic activators require SIRT1 to mediate the in vivo effects in muscle and identified a structured activation domain. They demonstrated that miscommunication between the mitochondrial and nuclear genomes is a cause of age-related physiological decline and that relocalization of chromatin factors in response to DNA breaks may be a cause of aging.
David Sinclair | The Sinclair Lab (harvard.edu)
Sinclair believes that this technology though it is more than 10 years old will be the advance to claim your own life limit. “In 10 years, you will be able to go into a doctor’s office, get a pill, and head out.” Sinclair tell a reporter on NBC news. I don’t take that too literal. As we all know, the body breaks down all that we ingest and absorbs proteins and minerals, etc. individually. They would then be used where they are needed instead of where they are intended. “It is and will continue to be my life-long work to figure the epigenome out and get it to all that could benefit from its development.” Sinclair promises.
I believe that with the technology, effort, time and knowledge put into epigenetics, there will be great advances in my lifetime leading to a much more comfortable quality of life for many of the human race.
