Epigenetics: Turning Genes on and off

The genetic information used to build our bodies and keep them working properly is found in our DNA. That information is organized in the form of genes. Genes are instructions used to make proteins, which are the building blocks of all our cells. This process of using the information in DNA to make proteins is called gene expression. However, cells do not express all genes at all times, so our cells need a control system to tell them which genes to express (switch on) and which to switch off. That control system is called epigenetics and it is a very complex system.

One of the best understood parts of epigenetics is the process of DNA methylation. DNA methylation is performed by a protein called DNA methyltransferase (DNMT), which adds small chemical units called methyl groups (CH₃) to particular places in the DNA sequence (Figure 1). The methylation of the DNA in this way switches genes off. The more spots that are methylated, the more firmly “off” the switch is. Genes involved with maintaining health are increasingly turned off as we age. Turning health-related genes off leads to a greater likelihood of developing diseases as we age.

What Factors Turn Genes on and off?

Although the overall pattern of DNA methylation is similar in most people, the amount of methylation can be increased or decreased by what we eat, by our physical activities, by disease, and by exposure to chemicals or pollutants in the environment. Atmospheric pollution is a concerning problem in many areas of the world and particularly in major cities. This pollution is mostly due to the burning of fossil fuels by factories, power plants, cars, and heaters, and also caused by cigarette smoke. For years, atmospheric pollution has been linked to diseases of the respiratory system, but now that scientists have some understanding of epigenetics, the way these pollutants affect us is better understood. For instance, changes in DNA methylation were identified in diseases related to lung functions in adults exposed to a pollutant called nitrogen dioxide [1]. Also, in children and adolescents, cases of asthma linked to exposure to atmospheric pollution were associated with changes in methylation levels that could occur before birth, showing that pollution can have long-lasting effects on people’s health [2].

Fortunately, substances naturally contained in certain foods can combat some of the negative effects of pollution on the body. Several studies have shown that certain vitamins, particularly those of the vitamin B group, can decrease the damage to cells caused by atmospheric pollution. These vitamins act by maintaining a normal level of DNA methylation (Figure 2) [3].

What Is the Epigenetic Clock?

How old are you? This question is easily answered by counting the years since your birth (your chronological age), but what about your biological age? Biological age indicates where a person is in their lifespan, based on the damages their cells have sustained. It is interesting that some people look younger than others at the same chronological age, suggesting that factors other than time are at work to cause cells to age. One method researchers have been using to estimate biological age is called the epigenetic clock [3]. The epigenetic clock is based on the levels of DNA methylation. As we mentioned earlier, as we age, methylation of our genes, including the genes that keep us healthy and young, increases. So, by measuring DNA methylation at a number of locations on the DNA from several different cells and tissues, and doing some fancy math on those results, scientists can use the epigenetic clock to determine a person’s biological age.

Biological age calculated using this method is highly correlated with chronological age [3], which tells us that the epigenetic clock is a good tool for calculating biological age. The epigenetic clock also predicts how quickly diseases like Alzheimer’s disease, high blood pressure, diabetes or cancer will get worse. So far, researchers have shown that high-risk lifestyles, like smoking or drinking alcohol, lead to a speeding up of biological aging. On the other hand, a healthy diet can slow down biological aging.

Vitamins B₉ and B₁₂

Our bodies need healthy food and a balanced diet to function efficiently. Fruits and vegetables are one of the main food groups containing vitamins. Vitamins are essential for growth, development, and cell function. This means that vitamins help the body to function properly. A long-term lack of a vitamin, which is called a vitamin deficiency, can cause serious symptoms. For example, bleeding gums can result from a lack of vitamin C, and a deficiency in vitamin A causes poor night vision.

B vitamins are important for cell metabolism. Vitamin B₉ is found in dark-green, leafy vegetables such as spinach, broccoli, asparagus and Brussels sprouts. B₉ helps with the synthesis of DNA and RNA, and it is also required for cell division, helping cell growth and development. A deficiency of vitamin B₉ can lead to anemia, which is a problem with blood cell development that leads to poor transport of oxygen and can cause tiredness and weakness. Good sources of vitamin B₁₂ are meat, fish, milk, cheese and eggs. Vitamin B₁₂ helps to keep blood and nerve cells healthy and also helps to make DNA. Vitamin B₁₂ deficiency can also cause anemia. Generally, most people get enough vitamin B₁₂ from a balanced diet. However, older adults and people who have a poor ability to absorb vitamins might benefit from vitamin supplementation, which is generally considered to be safe even at high doses.

Vitamins B₉ and B₁₂ Can Slow Down the Epigenetic Clock

Both vitamins B₉ and B₁₂ are involved in biochemical reactions that can increase DNA methylation. However, tiny differences in DNA that naturally exist between individuals, called single nucleotide polymorphisms (SNPs) can also play a role in gene methylation. People with a “normal” SNP for the availability of methyl groups have higher methylation levels, but people with a “faulty” SNP in the same location on the DNA have less methylation occurring.

To understand the impact of B vitamins on biological age, a group of 44 older adults (age 65–75) was studied for 2 years. The diets of study participants were supplemented with vitamins B₉ (400 μg/day) and B₁₂ (500 μg/day) for 2 years [4]. To evaluate biological aging, DNA methylation levels were analyzed from 353 locations in the DNA, and we put this data into an epigenetic calculator to tell us what their biological age was. In this way, the speed of the epigenetic clock of all participants was generated both before and after supplementation, so that we could compare their real age with their biological age.

Our results showed that, after supplementation, women who carried the normal SNP (the variant that produces a higher methylation activity) had epigenetic clocks that were running slower than those of women with the faulty SNP (Figure 3) [5]. However, the epigenetic clocks of women with the faulty SNP and men were not affected by vitamin supplementation. These results show that the effects of vitamins B₉ and B₁₂ appear to be gender and SNP-specific. Although there is no formal evidence for it, the methylation increase observed in women with the normal SNP could have turned off some specific pro-aging genes, with the result of limiting their biological aging over the time of the experiment.

Conclusion

Diet plays a role in epigenetic changes, especially in DNA methylation. By looking at the epigenetic clock, we found that vitamins B₉ and B₁₂ can slow down biological aging in a gender and SNP-specific manner. Although not everybody is affected by vitamins B₉ and B₁₂ supplementation in the same way, our results are encouraging because they mean we might eventually be able to help people to live longer, healthier lives by changing their diets. To achieve this goal, personalized balanced diets could be designed based on the analysis of people’s DNA methylation levels. But until we can do this, it is important that we all eat healthy foods, with plenty of vitamins, to keep our epigenetic clocks running properly!

Glossary

Gene Expression: ↑ The process by which DNA sequences are read to produce proteins.

Epigenetics: ↑ The biological mechanism in which gene expression is modified without changing DNA sequences, such as by methylation.

DNA Methylation: ↑ A biological process in which a methyl group (CH₃), is added to a DNA sequence. Methylation shuts off gene expression.

DNA Methyltransferase (DNMT): ↑ A protein capable of DNA methylation.

Methyl Group: ↑ A small molecule made of one carbon and three hydrogen atoms. It can be added to DNA through a reaction called methylation.

Biological Age: ↑ The age corresponding to environment factors like genetics, epigenetics, and lifestyle.

Epigenetic Clock: ↑ A test that calculates a person’s biological age using DNA methylation level measurements.

Single Nucleotide Polymorphism (SNP): ↑ A very small variation in a DNA sequence of an individual.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.