From the Guidelines
Epigenetics is the study of how behaviors and environment can cause changes that affect the way genes work without altering the DNA sequence itself, and it encompasses the ensemble of mechanisms that modulate gene expression programs, including DNA methylation, histone modification, and noncoding RNA, which can turn genes on or off and control how much protein is produced from a gene. These changes can be passed down to future generations but don't involve mutations to the genetic code 1. Epigenetic mechanisms are crucial in understanding how environmental factors like diet, stress, exercise, and exposure to toxins can trigger epigenetic changes, which can affect gene expression and potentially impact health outcomes 1. For example, identical twins with the same DNA can develop different traits or disease risks due to epigenetic differences that accumulate over their lifetimes.
Key Epigenetic Mechanisms
- DNA methylation: the addition of a methyl group to the 5th carbon of the pyrimidine ring of a cytosine (C) base juxtaposed to guanine (G) through a phosphate (p) bond (CpG), which can suppress gene transcription by blocking transcription factors from binding to promoter sequences 1
- Histone modification: changes to the histone proteins that DNA wraps around, which can affect gene expression by altering chromatin structure 1
- Noncoding RNA: RNA molecules that do not code for proteins but can regulate gene expression by interacting with DNA or other RNA molecules 1
Importance of Epigenetics
Understanding epigenetics helps explain why genetics alone doesn't determine health outcomes and provides insights into disease development, aging processes, and potential therapeutic targets 1. This field is important because it shows how our lifestyle choices can influence gene expression and potentially impact our children's health. The development of epigenetic clocks, which can track biological aging, has been a significant advancement in the field, and these clocks have been shown to be strongly correlated with chronological age and can accurately quantify an age-related phenotype or outcome 1.
Epigenetic Clocks
Epigenetic clocks are estimators built from epigenetic DNA methylation marks that are strongly correlated with chronological age or time, which can accurately quantify an age-related phenotype or outcome, or both 1. These clocks are generally built with a supervised machine learning method, such as a penalized regression, trained against chronological age to identify an informative and sparse predictive set of CpGs. The residual, or error from chronological age, is used as a marker for biological age of an individual.
Future Directions
Further research is needed to dissect the strengths and weaknesses of epigenetic clocks as a biomarker, in order to probe its biological significance, cellular mechanics, and epidemiological potential 1. This includes defining the current issues, suggesting what will aid unlocking future potential, and further exploring and defining any functionality, with the hopeful long-term benefit of increasing the “healthspan.”
From the Research
Definition of Epigenetics
- Epigenetics is defined as heritable changes in gene expression that are not attributable to alterations in the sequence of DNA 2, 3, 4, 5, 6
- These changes can occur without a change in DNA sequence and are critical components in the normal development and growth of cells 3, 4, 5, 6
Epigenetic Mechanisms
- The predominant epigenetic mechanisms include DNA methylation, modifications to chromatin, loss of imprinting, and non-coding RNA 2
- DNA methylation is involved in transcriptional silencing of genes, regulation of expression of imprinted genes, and silencing of genes located on the inactive X chromosome 6
- Histone modification and RNA-associated silencing are also intricately related in initiating and sustaining epigenetic modifications 6
Effects of Epigenetics on Health
- Epigenetic regulation of gene expression appears to have long-term effects and wide-ranging effects on health 2
- Aberrant epigenetic patterns have been linked to a number of diseases, including cancer, genetic disorders, and autoimmune diseases 2, 3, 4, 5
- Diet and environmental exposures may potentially alter the level and scope of epigenetic regulation, thus explaining correlations between lifestyle and risk of disease 2
Clinical Applications of Epigenetics
- Epigenetic modifications of DNA in cancer and precancerous lesions offer hope and the promise of novel biomarkers for early cancer detection, prediction, prognosis, and response to treatment 2
- Reversal of epigenetic changes represents a potential target of novel therapeutic strategies and medication design 2
- Epigenetic approaches may be used to targeted treatment of genetic conditions, such as fragile X syndrome 5