Epigenetics, DNA methylation and its connection with aging
Throughout history, people have been curious about what makes us human. According to social scientists, our environments shape or nurture who we are. On the other hand, biologists would argue that everything in nature is determined by our genes, which are “set in stone” and imprinted in us from birth.
So, is nurture or nature what defines who we are? Or is it both? The answer might be found in epigenetics.
What is epigenetics?
Epigenetics is a field of study related to how nature and nurture interact. “Epi” means “above” in Greek, so epigenetics literally translates to “above genetics”.
Simply put, genes contain instructions that communicate how often, when, and which proteins are created. Proteins are necessary for healthy cells, which in turn are building blocks of all living things. Furthermore, genes play an important role in our health, as it determines how likely we are to develop genetic diseases.
How behaviour and environment causes epigenetic changes
Epigenetics is the study of how our behaviour and environment cause changes to our gene expression through for example diet, physical activity, and exposure to harmful substances (1). Epigenetics can turn genes on (gene activation) or off (gene inhibition). Moreover, epigenetic changes start already in the embryo (1). All the cells have the same genes and start from one genome. As the cells divide, some genes are activated, others are inhibited, and as a result the cells look and act differently. For example, some cells become heart cells, other muscle cells, or liver cells. Epigenetics allows for a heart cell to activate genes that allow for the cell to become a heart cell and inhibit other genes (1).
Reversibility of epigenetic changes
Unlike genetic changes, epigenetic changes are reversible and do not change the DNA sequence but can alter how our body interprets it (1). For example, it has been reported that cigarette smoking may result in epigenetic changes (2). A recent study investigated if these changes are permanent and if no, can they be reversed. At certain parts of the DNA, smokers tend to have less DNA methylation (see below) compared to non-smokers. After quitting smoking, former smokers can begin to have increased DNA methylation compared to smokers. Eventually, former smokers can reach to DNA methylation level of non-smokers. In some cases, this can occur in less than one year but how long it takes depends on the frequency and the duration of smoking before quitting (2).
The reversibility of epigenetic changes is what makes it an attractive area of research in the field of longevity.
Epigenetics and biological age
Epigenetics is at the core of epigenetic clocks and crucial for studying biological age. Chronological age is the age based on our birthday. Biological age, on the other hand, is based on the age that our cells, tissues, and organs have (4). (Read more about biological age here). Early models of epigenetic clocks were based on measuring the telomere length (more about telomeres read here) and more recent models are based on DNA methylation (a form of epigenetic change). Understanding these processes can help understand and validate biological age interventions (4).
How epigenetic changes work?
Epigenetic changes are natural and essential to many functions in the body, but if they occur improperly, there can be major adverse health and behavioral effects (5). Epigenetic changes are biological processes affecting gene expression in different ways. Some types of epigenetic changes include:
- DNA methylation
- Histone modification
- Non-coding RNA
Perhaps the best studied epigenetic change, is DNA methylation (5). This is the addition (methylation) or removal (demethylation) of a methyl group (CH3) to DNA. That is a normal and vital process for our bodies to function, if it is kept at optimal levels. Both under (hypomethylation) and over methylation (hypermethylation) can be harmful and can play role in autoimmune diseases, neurological diseases, cancer, and aging.
For example, DNA methylation is harmful when tumour suppressor genes are methylated (6). When DNA methylation occurs in the tumour suppressors, the methyl group prevents gene expression, causing cellular function to be disrupted. The gene is still there, but it’s “silent”, therefore, it does not do what it is supposed to do- suppress the tumour. On the other hand, not enough methylation can cause genomic instability and cell transformation (more about genomic instability read here Hallmarks of Aging – Part 1 – nem.health) (6).
Unlike genetic alterations, however, DNA methylation is reversible, and thus is very attractive to study for development of new therapeutics (6).
DNA Methylation and aging
The epigenetics changes throughout life. The epigenetics at birth are different than the epigenetics in childhood or adulthood. A study investigated the DNA methylation of different sites of the DNA in newborn vs 26 year old vs a centenarian (103 years old) (7). The level of DNA methylation decreases with age. The newborn had the highest DNA methylation level, followed by the 26 year old, and the centenarian had the lowest DNA methylation level (7).
Additional studies comparing DNA methylation levels from individuals of different ages showed a significant decrease in global DNA methylation with age. However, this loss was less pronounced in centenarians (People living over 100 years old) (8). Overall, these results support the idea that DNA methylation is involved in human aging and longevity (8).
The role of epigenetics in diseases and treatments
Although cancer has received the most attention, other diseases such as Alzheimer’s and arteriosclerosis have also been linked to environmental factors, making them appealing areas for epigenetic research (5). It is thought that epigenetics have huge potential to help solve some of the most difficult to treat diseases and several initiatives around the world are currently investigating the epigenome (9) (10).
Understanding epigenetics could help us better understand how our cells and bodies work and that may enable us to develop more sophisticated treatments for diseases.
In conclusion, the study of epigenetics is a dynamic and exciting field, and the measurement of biological age is especially interesting. Analysing, and understanding your biological age might be a good start to help you improve your health and lifestyle. At NEM we use biological age assessments in clinical practice to help guide our clients to better and longer lives, and the further study of epigenetics is a promising area that may hold the key to unlocking the mysteries of disease, aging and longevity.
1. CDC. What is Epigenetics? | CDC [Internet]. Centers for Disease Control and Prevention. 2022 [cited 2022 Dec 26]. Available from: https://www.cdc.gov/genomics/disease/epigenetics.htm
2. McCartney DL, Stevenson AJ, Hillary RF, Walker RM, Bermingham ML, Morris SW, et al. Epigenetic signatures of starting and stopping smoking. EBioMedicine. 2018 Nov 1;37:214–20.
3. How do genes direct the production of proteins?: MedlinePlus Genetics [Internet]. [cited 2022 Dec 26]. Available from: https://medlineplus.gov/genetics/understanding/howgeneswork/makingprotein/
4. The epigenetics of aging: What the body’s hands of time tell us [Internet]. National Institute on Aging. 2021 [cited 2023 Jan 29]. Available from: https://www.nia.nih.gov/news/epigenetics-aging-what-bodys-hands-time-tell-us
5. Weinhold B. Epigenetics: The Science of Change. Environ Health Perspect. 2006 Mar;114(3):A160–7.
6. Kandi V, Vadakedath S. Effect of DNA Methylation in Various Diseases and the Probable Protective Role of Nutrition: A Mini-Review. Cureus. 7(8):e309.
7. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci. 2012 Jun 26;109(26):10522–7.
8. Marcos-Pérez D, Saenz-Antoñanzas A, Matheu A. Centenarians as models of healthy aging: Example of REST. Ageing Res Rev. 2021 Sep 1;70:101392.
9. Abbott A. Europe to map the human epigenome. Nature. 2011 Sep 1;477(7366):518–518.
10.Brena RM, Huang THM, Plass C. Toward a human epigenome. Nat Genet. 2006 Dec;38(12):1359–60.