This article aims to provide a scientific and evidence based account of the Epigenetic potential of Physical Exercise. Epigenetics might be a terminology that is greek to many of my readers.Ergo, I shall give you a brief overview of what it is. Epigenetics literally means "On top of Genetics". In other words it is a molecular level physiological process that causes external modification to physical structure of DNA without altering the DNA Sequence. These external or structural modification of DNA may "turn on" or "turn off" genes.
There are four molecular mechanisms that govern epigenetic alternations to DNA.
1) DNA Methylation- It is simply the addition of a methyle group or a chemical cap to a part of the DNA molecule , which may prevent the expression of some genes.
2) Histone Acetylation or modifiction- Histones are proteins around which DNA wraps. If histone squeezes the DNA tightly the DNA can not be read by the transcriptional proteins of the cell.Modifications that relax the histones makes the DNA accessible to Transcriptional Proteins that read genes.
3)RNA Silencing- It is a type of post transcriptional gene modification during which the expression of one or more genes is down regulated by small non-coding stretches of RNA called mRNA.
4)Chromatin remodeling- It is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins and thereby control gene expression.
It is in fact due to epigentics that a cardiac muscle cell differs from smooth muscle cell in both morphologically and physiologically, despite having exactly same DNA.
Epigenetics can be divided into two,Positive and Negative Epigenetics. An example for negative epigenetics is that an epigenetic change that mutes a tumor Suppressor gene eg:APC gene could lead to colo-rectal cancer in human.
It has been postulated that lifestyle, diet and exercise could alos cause promising and positive epigenetics. However, it is only very recently the scientific community could bring out statistically significant evidence for exercise and life style induced positive epigenetics. An approach to exercise and lifestyle modification should be focused to elicit positive epigenetics. As the research progress we may be able to develop scientific methods to design personalized exercise programs and lifestyle and dietary modifications to positively prevent the epigenetic inheritance of hereditary diseases.
In this article I will provide a brief overview of the current research based evidence of Physical exercise induced epigenetics and its scope.
Exercise may delay the onset of diabetes by enhancing the DNA Hypomethylation and expression of genes involved in oxidative metabolism and glucose regulation. A 2012 study published in the journal Cell metabolism reported that acute exercise elicits changes in gene expressions that trigger structural and metabolic adaptation in skeletal muscles. The changes in gene expression in particular expression on PGC1-alpha( Transcription factor crucial in Muscle cell oxidation), PDK-4( important in glucose metabolism) and PPAR-delta( Transcription factor)together with marked hypomethylation of respective promoters. The researchers concluded that exercise induced acute gene activation is associated with dynamic changes in DNA methylation in skeletal muscles and suggests that DNA hypomethylation is an early event in contraction- induced gene activation ( Romain Barres et all 2012).
A Cross sectional study conducted by Coyle YM et all in 2007 reported that physical activity reduces breast cancer risk by enhancing promoter hypermethylation of tumor suppressor genes such as APC in non-malignant breast tissue. It implies the fact that physical exercise in particular aerobic activity could be a good prophylaxis in women susceptible to breast cancer.
An another 2012 study conducted to determine the effect of physical activity on DNA methylation and to predict the consequences of these effects concerning gene expression and breast cancer survival concluded that increasing physical activity after breast cancer diagnosis may affect epigenetic regulation of tumor suppressor genes which have favorable impacts on survival outcomes of breast cancer patient. In this study patients diagnosed with breast cancer underwent 6 moths of moderate intensity aerobic exercise. Positive changes in DNA methylation in peripheral blood leukocytes where detected in 43 genes from a panel of 14495 genes.The study reported that exercise induced hypomethylation of L3MBTL1 gene which is a putative tumor suppressor gene with known function to repress chromatin for transcription, which is activated mainly in germline stem cells.
Currently the research data are limited to only a number of studies. However, it is certain that more and more studies will come in the nearest future to corroborate the notion of considering systematic and personalized exercise as a means for eliciting positive epigenetics. These studies supports the fact that exercise is the less expensive and non-invasive prophylaxis for a large number of diseases and conditions as well as a potentially indispensable part of a comprehensive treatment plan of a number of oncoglogic conditions and metabolic syndromes.
I hope my fellow exercise professionals , clinical exercise specialists and all those who read this article will find it informative.
Siby C Chacko MPE ( Exercise Physiology)
References
1) R Barres, J Yan, B Egan, Jonas T T, Morten R, T Fritz, Kenneth C, A Crook, Donal J O , Juleen R Z, Acute Exercise Remodels Promoter methylation in Skeletal Muscles. Cell Metab. 7,15(3):405-11 (2012).
2) Coyle Ym ,Xie Xj,Lewis CM, Bu D, Euhus DM, Role of Physical activity in modulating breast cancer as defined by APC and RASSF1A promoter hypermethylation in non-malignant breast tissue. Cancer, epidem,bio-mrk.Prev.16(2)192-6 ( 2007).
3) Zeng H, Irwin ML, Lu L, Risch H, Mayne S, Mu L, Deng Q, Scarampi L, Mitidieri M, Katsaros D, Yu H , Physical activity and breast cancer survival:An epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1. Brest cancer reser.treat.133(1):127-35(2012)
