DNA methylation in fetuses

DNA methylation is one of the most reliable, and therefore important biomarkers of aging.

DNA methylation is a biochemical process in which a methyl group (-CH3) is added to the DNA molecule, typically at cytosine residues in a CpG dinucleotide context, resulting in 5-methylcytosine (5mC). DNA methylation is a form of epigenetic modification that can alter gene expression without changing the DNA sequence itself.

There is evidence to suggest that DNA methylation plays a role in aging. It is unlikely to be the cause of aging, but a sign of aging. Specifically, as we age, there is a general tendency for DNA methylation patterns to change, with some regions becoming more methylated while others becoming less methylated. These changes in DNA methylation patterns can affect gene expression and contribute to age-related diseases and conditions.

DNA methylation as an epigenetic clock

DNA methylation is a good predictor of age. One well-studied example of age-related DNA methylation changes is the phenomenon of “epigenetic clocks”. These are DNA methylation-based biomarkers that predict chronological age with high accuracy across different tissues and organisms. Several different epigenetic clocks have been developed, each based on different sets of CpG sites that show a consistent pattern of methylation changes with age.

In addition to age-related changes in global DNA methylation patterns, specific genes and pathways can be affected by altered DNA methylation in aging. For example, certain tumor suppressor genes and genes involved in cellular senescence have been found to become hypermethylated with age, leading to decreased expression and potentially contributing to cancer and age-related functional decline.

DNA methylation begins before we are born

DNA methylation begins very early. DNA methylation in fetuses is a dynamic process that begins early in development and continues throughout life. During fetal development, DNA methylation patterns are established during gametogenesis and early embryonic development (El Hajj and Haaf, 2013). By the time of birth, the methylation patterns are largely established, although some degree of plasticity remains. Therefore, interventions that improve maternal health during pregnancy may have the potential to improve DNA methylation patterns in fetuses and prevent adverse health outcomes later in life.

Can the parents affect the pace of DNA methylation?

Based on recent research, several factors can impact DNA methylation in fetuses, and some of them may be modifiable by maternal interventions, which is promising for parents.

Here are some findings from the studies:

1. Maternal nutrition: A mother’s diet can affect the methylation status of her offspring, as demonstrated in animal studies (Novakovic and Saffery, 2012). For example, maternal undernutrition during pregnancy has been shown to cause hypomethylation in the placenta and fetal liver of rats (Sferruzzi-Perri et al., 2019). On the other hand, maternal overnutrition has been linked to hypermethylation and altered expression of metabolic genes in the offspring (Novakovic and Saffery, 2012). Therefore, it is recommended that pregnant women follow a balanced and healthy diet to support fetal development.
2. Maternal stress: Prenatal stress has been associated with altered DNA methylation patterns in offspring, particularly in genes involved in neurodevelopment and stress response (Keverne et al., 1996). For a fetus, the only proper information to influence development is the information transmitted from the mother. A stressful environment will shape the DNA methylation and other epigenetic switches of the unborn child. Therefore, pregnant women need to manage their stress levels through relaxation techniques, exercise, and social support. It is
3. Maternal exposure to toxins: Exposure to environmental toxins such as cigarette smoke, air pollution, and pesticides have been linked to DNA methylation changes in fetuses and adverse health outcomes later in life (Novakovic and Saffery, 2012). Therefore, pregnant women should avoid exposure to such toxins as much as possible.