Epigenetics is the study of changes in organisms caused by modification of gene expression and cause cells to differentiate into specialised cells (skin cells, liver cells, brain cells etc) 3 without altering the DNA base sequence. 1 These changes involve genes becoming switched on or off due to the addition or removal of chemical groups to or from the DNA and results in the change in phenotype but not genotype.
2 The epigenetic processes that are involved are DNA methylation, histone modification and non-coding RNA. 3 However, DNA methylation is one of the main processes that control gene expression. Using an epigenetic clock, researchers at the Babraham Institute have managed to predict ages by studying the changes that epigenetic processes cause. The models have been useful to see if diet, lifestyle or medicines can speed up or slow down ageing processes. DNA methylation is the addition of a methyl group (-CH3) near a CpG site (this is where a cytosine group and guanine are next to each other) in the DNA code for a gene.
The attaching of a methyl group causes a change in the DNA structure as proteins and enzymes which are required for transcription can’t bind to the gene, resulting it to become repressed. The expressions of these genes can also be influenced by lifestyle factors such as nutrition and exercise as they increase the methylation of certain genes which lead to a range of health problems. 5DNA demethylation is needed for epigenetic reprogramming of genes. This involves is the removing a methyl group and this can either be passive or active (can also be both). Passive DNA demethylation takes place on newly synthesized DNA strands during replication whereas active DNA demethylation occurs by removing 5-methylcytosine.
6Histone ModificationHistones are proteins which wrapped around DNA to form chromatin. Chromatin make up chromosomes so they either be highly condensed or less condensed, and this affects proteins and enzymes needed for transcription to access and bind to the DNA. This form of epigenetic modification includes the addition or removal of acetyl groups(-COCH3). When an acetyl group is attached to a histone it’s become acetylated, making the chromatin less dense. This allows proteins involved in transcription to bind to the DNA to transcribe the gene so that it can be activated. The removal of acetyl groups from histones are called deacetylated and this cause the chromatin to become highly condense. This makes it harder for transcription proteins to access the genes and bind to it, resulting in genes becoming repressed.
5Non-coding RNANon-coding RNA (ncRNA) is a functional RNA which is transcribed but not translated into proteins. The ncRNAs include miRNA, siRNA, piRNA and IncRNA and their function is to regulate gene expression at a transcriptional level as well as the post transcriptional level. The ncRNA are divided in two main groups; short ncRNAs which are greater than 30 nts and long ncRNAs which are less than 200 nts, and they both play a role in heterochromatin formation, DNA methylation, histone modification and gene silencing. Short ncRNAs are divided further into three major groups which are microRNAs (miRNAs), short interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs). 7LifestyleExercise lowers the risk of chronic diseases and help maintain energy balance.
Recent studies have shown the links between exercise and methylation of specific genes related chronic disease risk factors. For example, exercise is responsible for methylation of genes which are responsible for secretion of pro-inflammatory cytokines. Pro-inflammatory cytokines are a cause of chronic inflammation and methylation of the gene reduces the risk of cancer.Exercise can also change the way the body stores fat.
A recent study was carried out which involved looking at a six-month exercise programme which influences DNA methylation in previously sedentary men to see the impacts on fat storage and metabolism. The programme consisted of a weekly one 60-minute spinning class and two 60-minute aerobic session. The exercises had caused methylation in genes related to obesity and type 2 diabetes. From this they were able to conclude that exercise reduces the risk of obesity and type 2 diabetes as changes were present in families with and without history of these two factors.
11 An improvement in metabolism means that the body can remove toxins more effectively from the body, circulate blood around more efficiently which means we are able to look younger due to the increase in oxygen intake and removal of waste products. 12Aging -Epigenetic clock in HumansAge is distinguished between biological age and chronological age. Biological age is a measure of how well your body functions whereas chronological age is how old you are. Using an epigenetic clock both biological and chronological age can be predicted.
This has now allowed scientists to accurately predict +/- 3.6 years from any tissue or fluid in the human body- this is the chronological age. 8 An epigenetic clock uses changes at 329 points out of 23 million places on the DNA to predict biological age. This allows researchers to investigate ageing. 1An experiment published by Steve Horvath looked at the epigenetic clock in humans.
He conducted this experiment because it’s not known whether the results gained about age is biologically a meaningful measure. DNA methylation can predict age across a wide range of human tissues and cell types accurately. He developed a multi-tissue age predictor which used 8,000 samples from ’82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types’. From this he was able to find out that DNA methylation age is close to 0 for embryonic and induced pluripotent stem cells, it gives rise to age acceleration which can easily be inherited, and this model can be used on chimpanzee tissue. He also used the age predicter to analyse 6,000 cancer samples from 32 datasets. and has been able to show age acceleration with an average of 36 years. From this he has been able to conclude that ‘DNA methylation age measures the cumulative effect of an epigenetic maintenance system’.
9The benefits of this method are that its highly applicable to any sample of tissue or fluid in the human body to predict biological age as it uses the same markers, regardless of the DNA source. It allows different types of tissues to be tested e.g. different mammals.
9 However, there is still a median error of 3.6 years. Also, if other researchers wanted to observe how changes to molecular components can slow down or speed up ageing it would be impossible to carry out on humans due to ethical and practical issues. 8Aging- Epigenetic Clock in MiceDNA methylation is essential for the growth of cells in mammals, so researchers have found epigenetic ageing clock in mice and have been able to use a computer model (epigenetic clock) to display changes in DNA methylation at 329 sites in the genome to predict the age of a mouse. The researchers at the Babraham I have been able to predict age with the mouse with an accuracy of +/- 3.
3 weeks. 1This model has also been used to show how some changes in lifestyle can cause the clock to speed up. For example, ovaries in female mice becoming removed by the group of researchers caused the clock to speed up. 4Reprogramming Cells Three different research groups in June 2007 showed reprograming can reverse cells to a youthful state. However, reprogramming only works at a cellular level. This research was carried out by researchers taking old skin cells from adult mice and adding 4 proteins called Yamanaka factors.
The reprogramed cells had lost all its age features and acted as totipotent cells rather than skin cells. Reprogramming has benefits such as being able to implant the newly reprogrammed cells into female mice to form an embryo which is able to grow healthy. However, the main problem which has risen from reprogramming has meant that all the cells of that feature i.e. skin cells would lose all its features and become identity-less like embryo cells.
This makes the treatment not as useful for humans, so researchers are trying to find if it’s possible to reverse aging without changing all the cells into embryonic-like cells. 10Conclusion There isn’t much research on the field of epigenetics as most studies have only been done at a cellular level rather than being applied on humans. But from the studies which have been conducted the benefits of the research have meant that humans aren’t harmed as experiments are being done on rats as well as chimpanzee tissues. Other benefits gained from research is that scientists are now able to reprogram cells to be become embryo like cells. The only drawback to this is that it turns all the cells of that tissue to embryonic like cells. However, this causes an ethical issue because some people may think it’s unfair to test on animals as they don’t have a say.
And another problem is that the research is very limiting as it can only be done at a cellular level. Fortunately, we are still able to control our lifestyle by implementing more exercise and changing our diets. This has meant that there will be an improvement in our metabolism which contributes to helping us looking and feeling younger.