Connecting genomic and environmental factors that affect health
Epigenetics studies heritable and reversible changes that occur in gene function without modifying the DNA sequence.
Physical and mental health depends not only on the modifications in the DNA code inherited from our ancestors (genetics), but also on the dynamic interaction between our genes and the environment, even if the genetic code is not altered (epigenetics).
Epigenetic changes are reversible and depend on the quality of the interaction between the individual and his or her environment, and therefore we can act on them to improve our health.
An illustrative example of the influence of epigenetics is seen in studies of monozygotic identical twins. Although they share an identical DNA sequence, both develop a very different predisposition to certain types of diseases.
This is largely explained by the fact that both have been exposed to very different stimuli (diet, social life, hobbies, vices, stress, etc.), and their genomes, although identical, are expressed differently.
Epigenetics plays a fundamental role in the development of prevalent diseases (cardiovascular, cancer, and brain diseases). Thus, for example, mechanisms such as memory and learning, cognitive impairment associated with old age or behavioural disorders are largely epigenetically regulated.
EuroEspes is developing a series of epigenetic biomarkers that allow for both the detection of diseases and the monitoring of the response to the different treatments provided to the patient:
In processes that involve tumours and neurodegeneration, there are lower levels of global DNA methylation. Therefore, this biomarker makes it possible to detect whether these global methylation levels correspond to those of a healthy person, or whether they present abnormal levels compatible with tumour and neurodegenerative processes. Furthermore, treatment with AtreMorine, an epinutraceutical that increases Dopamine levels, increases global methylation levels in Parkinson's patients.
The pyrosequencing technique allows for the measurement of methylation levels in certain regions of some genes, enabling the diagnosis of certain pathologies (Parkinson's, Alzheimer's, colorectal cancer, etc.). For example, Septin 9 methylation is altered in colorectal cancer. The study of Septin 9 methylation levels is a biomarker for screening and early diagnosis of this type of cancer (approved by the FDA and the EU).
Changes in methylation levels often lead to changes in gene expression. Thus, the study of the expression levels of important genes in certain pathologies is also a new biomarker.
The expression levels of certain miRNAs are associated with different pathologies. For example, an epigenetic signature of 12 miRNAs is a biomarker for the early diagnosis of thyroid cancer and another signature of 8 miRNAs is used for the diagnosis of lung cancer.
Individual differences in drug response and metabolism are explained by both the genetics and epigenetics of individuals.
For example, smoking has been reported to affect the methylation of the CYP1A1 gene, which is involved in drug metabolism. In addition, the methylation of different genes in tumour processes affects the response to different chemotherapeutic agents. For example, MGMT methylation levels are related to a glioma patient’s response to chemotherapy.
In this way, the combination of genetic and epigenetic studies is a fundamental pillar of personalised medicine and allows better treatment of patients, avoiding ineffective or even toxic drugs.
Among the R&D projects of the EuroEspes Department of Medical Epigenetics is the study of the epigenetic changes that occur in the genes involved in drug metabolism and their association with the response to these treatments .
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Epigenetics is at the forefront in the prevention and treatment of multiple diseases, emerging as the future of medicine. As the particular epigenetic changes that distinguish each pathological entity are elucidated, the doors will open to a better understanding of the underlying mechanisms, allowing us to delineate more effective therapeutic strategies to safeguard the health and well-being of the population.
The epigenome represents the complete set of epigenetic information of an organism. Epigenetic profiles play a crucial role in the pathogenesis of chronic non-communicable diseases, such as cardiovascular diseases, metabolic disorders, obesity, autoimmune diseases, inflammatory diseases, cancer and the aging process.
The genotype represents the genetic load that we carry, while the phenotype corresponds to the observable manifestation of those genes, and it is here that we can exert influence. Epigenetics encompasses all the mechanisms that alter gene expression without causing changes in its DNA sequence.
Indeed, evidence has been obtained confirming the fundamental role of epigenetics in the aging process, given that such modifications between different stages of life affect a wide range of genes. In the long term, it seems feasible to prolong life, since changes in external behaviors could have an impact on the modification of the epigenome.