Epigenetics
Original Editor - Lucinda hampton
Top Contributors - Nivedita Raut, Lucinda hampton, Khloud Shreif, Carina Therese Magtibay, Kim Jackson and Chelsea Mclene
Introduction
Epigenetics is a fascinating field of science that explores how our environment and lifestyle choices can influence the way our genes behave. While our DNA provides the genetic blueprint for our body, epigenetics determines how these blueprints are read and executed. This dynamic interaction between our genes and the environment can affect everything from how we age to our susceptibility to certain diseases.
What is Epigenetics?
Epigenetics is the study of heritable and stable changes in gene expression that occur through adjustments in the chromosome rather than in the DNA sequence. They do not directly alter the DNA sequence, rather epigenetic mechanisms are able to regulate gene expression through chemical modifications of DNA bases and changes to the chromosomal superstructure.[1]
Epigenetics affect which genes are expressed, and subsequently, whether the cells should produce relevant proteins, e.g. determining a cell’s specialisation such as skin cell, blood cell, hair cell, liver cells, etc. These effects play a role both as a foetus develops through gene expression (active) or repression (dormant), and also through nurture with environmental stimuli having the ability to cause genes to be turned off or turned on.[2] The different combinations of genes that are turned on or off is what makes each one of us unique. For example, if we have brown or black hair, how sociable you are, how an oyster tastes to us. Additionally, there are indications that some epigenetic changes can be inherited.[2]
Image 1: Depicts genome changes that regulate gene activity without changing DNA sequence.
Epigenetics Mechanisms
Epigenetic changes effects work in different ways to bring about gene expression. Types of epigenetic changes include:
- DNA Methylation: refers to a chemical reaction in the body in which a small molecule called a methyl group gets added to DNA, proteins, or other molecules. The addition of methyl groups can affect how some molecules act in the body. In DNA the group is usually added to specific places, blocking the proteins that attach to DNA to “read” the gene. When this chemical group is removed the process called is called demethylation. In most cases, methylation turns genes “off” and demethylation turns genes “on.”
- Histone modification: DNA wraps around histones (which are proteins). If the histones are wrapped tightly around the DNA they cannot be accessed by proteins that “read” the gene. The genes that are wrapped around histones are turned “off” and the genes that are not wrapped around histones and are turned “on.” Chemical groups can be added or removed from histones and change whether a gene is unwrapped ("on") or wrapped (“off”).
- Non-coding RNA: DNA directs for making coding and non-coding RNA. Coding RNA is used to make proteins. Non-coding RNA helps control gene expression which it does attaching to coding RNA, along with certain proteins, to break down the coding RNA so that it cannot be used to make proteins. Non-coding RNA may also recruit proteins to modify histones to turn genes “on” or “off.”[3]
Epigenetics began over 60 years ago. During the 1970s it started becoming more prominent with the arrival of molecular biology and during the last 10–15 years, has emerged as a stand-alone discipline complementary to genetics. [4]
Image 4: Depicts how poor maternal nutrition reduces PDX1 expression via histone modification, impacting beta cell development and diabetes risk.
Image 5: Explains how DNA carries epigenetic tags that regulate gene activity; in tumors, excessive CpG island methylation (CIMP) can silence key genes that protect against cancer.
For a brief explanation watch this 5 minute video.
The Epigenetic Clock and Aging
Aging is one of the most visible effects of epigenetic changes. Scientists have discovered that certain epigenetic modifications accumulate as we age, affecting how our cells function. This "epigenetic clock" can provide insights into biological age, which may differ from chronological age.[6] Lifestyle factors such as diet, stress, exercise, and exposure to environmental toxins can speed up or slow down this clock, illustrating how closely our environment is linked to our genetic expression.[7]
Recent advancements have introduced sophisticated tools to measure the pace of biological aging through epigenetic markers. One such tool, the DunedinPACE clock[8], is based on DNA methylation patterns and provides an estimate of how quickly an individual's biological systems are aging relative to their chronological age. This epigenetic clock is used to assess the cumulative impact of lifestyle factors like physical activity, diet, and stress on biological aging. Studies show that individuals with slower DunedinPACE rates tend to have better overall health outcomes and lower risks for age-related diseases such as cardiovascular issues, diabetes, and cognitive decline.
Epigenetic Inheritance: Passing Changes to the Next Generation
One of the intriguing aspects of epigenetics is its potential for heritability. Epigenetic changes that occur due to lifestyle and environmental factors can sometimes be passed down to future generations[9]. This means that the choices we make today may not only impact our health but also influence the health of our children and grandchildren.[10]
As people age, the most significant influence on the epigenome is the environment. These include diet, smoking, physical activity and psychological stress[1]. For instance, studies have shown that the nutritional habits of parents can affect the epigenetic markers in their offspring, potentially shaping their health and susceptibility to diseases.
The field of nutriepigenomics looks into how food and epigenetics work together to influence health and wellbeing. eg studies have found that certain compounds within the foods we consume could protect against cancer by adjusting methyl marks on oncogenes or tumor suppressor genes[2].
Epigenetics and Exercise
It is now established that exercise is an important “medicine”. Examples of the role exercise can play in epigenetics include:
- Lifelong physical activity is associated with promoter hypo-methylation of genes involved in metabolism, myogenesis, contractile properties and oxidative stress resistance in aged human skeletal muscle[1]. Promoter regions are regions of DNA where transcription of a gene is initiated[2].
- Exercise is able to attenuate or reverse some of the high‐fat diet associated methylation patterns. Many of the genes found to be differentially methylated are implicated in metabolic functions, such as regulation of oxidative metabolism and glucose transportation, which have obvious significance for offspring.
- Exercise has also been shown to impact cognitive development, as hippocampal DNA methylation was found to be lower in exercise‐offspring. This shows that epigenetic intergenerational outcomes appear to be consistent with epigenetic alterations in people who regularly exercise[3].
- Studies show that acute and chronic exercise interventions induce a number of epigenetic modifications within the person exercising. In human skeletal muscle, both whole genome methylation and methylation of promoter regions of key metabolic genes decreased after completing a single‐session of cycling at 80% of VO2peak. Similarly, three months of regular single‐knee extension exercise showed genome‐wide DNA methylation alterations that were not observed in the untrained leg[3].
- Studies show that an important modulation of exercise exists on the epigenetics mechanisms, particularly in DNA methylation, specially of regular physical exercise[4].
Epigenetics and Disease Prevention
In conclusion, the field of epigenetics offers exciting prospects for advancing our understanding of disease prevention and management. Epigenetic modifications, influenced by lifestyle and environmental factors, hold the key to unlocking new therapeutic interventions. Research is actively exploring how drugs and dietary supplements can modify epigenetic marks to combat conditions such as cancer, Alzheimer’s disease, and metabolic disorders. Among these lifestyle factors, exercise stands out as a potent modulator of epigenetic changes. Regular physical activity has been demonstrated to enhance cardiovascular health, improve cognitive function, and support metabolic balance, thereby playing a critical role in disease prevention.[11] By integrating exercise into daily routines, individuals can positively influence their epigenetic profile and reduce the risk of various diseases, highlighting the significant impact of our lifestyle choices on our genetic expression and overall well-being.
References
- ↑ 1.0 1.1 1.2 Al Aboud NM, Tupper C, Jialal I. Genetics, epigenetic mechanism. Available:https://www.ncbi.nlm.nih.gov/books/NBK532999/ (accessed 25.7.2022)
- ↑ 2.0 2.1 2.2 2.3 Ashe Alyson, Colot Vincent and Oldroyd Benjamin P. 2021How does epigenetics influence the course of evolution?Phil. Trans. R. Soc. B37620200111
- ↑ 3.0 3.1 3.2 CDC Epigenetics Available:https://www.cdc.gov/genomics/disease/epigenetics.htm (accessed 26.7.2022)
- ↑ 4.0 4.1 W.W. Weber, in Comprehensive Medicinal Chemistry II, 2007 Available:https://www.sciencedirect.com/referencework/9780080450445/comprehensive-medicinal-chemistry-ii (accessed 26.7.2022)
- ↑ Carlos Guerrero-Bosagna. What is epigenetics. Available from: https://m.youtube.com/watch?v=_aAhcNjmvhc[last accessed 28/7/2022]
- ↑ Heyn H, Moran S, Esteller M. Epigenetic aging: More than just a clock when it comes to cancer. Cancer Res. 2017;77(19):5129-5133.
- ↑ Fedor Galkin, Olga Kovalchuk, Diana Koldasbayeva, Alex Zhavoronkov, Evelyne Bischof, Stress, diet, exercise: Common environmental factors and their impact on epigenetic age, Ageing Research Reviews, Volume 88,2023,101956, ISSN 1568-1637, https://doi.org/10.1016/j.arr.2023.101956.
- ↑ Brooks A, Vanhoutte D, Edwards M, et al. Advances in epigenetic biomarkers for aging: The role of the DunedinPACE clock. Mech Ageing Dev. 2023;207:111694.
- ↑ Stein, A. D (2004-07-28). Intrauterine famine exposure and body proportions at birth: the Dutch Hunger Winter". International Journal of Epidemiology. 33 (4): 831–836.
- ↑ Terence YC Pang, Annabel K Short, Timothy W Bredy, Anthony J Hannan, Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes, Current Opinion in Behavioral Sciences, Volume 14, 2017, Pages 140-147, ISSN 2352-1546, https://doi.org/10.1016/j.cobeha.2017.02.007.
- ↑ Guiling Wu, Xing Zhang, Feng Gao, The epigenetic landscape of exercise in cardiac health and disease, Journal of Sport and Health Science, Volume 10, Issue 6, 2021, Pages 648-659, ISSN 2095-2546, https://doi.org/10.1016/j.jshs.2020.12.003.