Epigenetic Alterations

Epigenetic alterations occur in the chemical modifications of DNA or the proteins associated with it rather than changes to the DNA sequence itself.

These modifications, also known as epigenetic marks, can turn genes on or off, influencing how our cells function and our overall health and longevity.

The epigenome is often compared to software, while the DNA is the hardware. The software provides the hardware with information on how to express genes to suit the cell’s purpose. For example, it differentiates a skin cell from a heart cell, even though they are both made of the same genetic material.

One of the most remarkable features of the epigenome is that it responds to both internal and external factors. It can be beneficially modified with bioactive nutrition compounds found in certain foods, such as isothiocyanates in broccoli and other cruciferous vegetables, genistein in soybean, and resveratrol in red grapes and some other purple foods.

These compounds can positively affect the epigenetic modifications of genes that regulate metabolism, inflammation, oxidative stress, and other processes crucial to our health.

However, the epigenome can also be negatively affected by environmental toxins, such as air pollution, heavy metals, pesticides, and other harmful chemicals, and stressful life events, such as trauma or chronic stress. These exposures can lead to changes in the epigenetic marks on DNA, which can alter gene expression and contribute to a range of health problems, including ageing.

Ageing is associated with alterations in the epigenetic marks, particularly DNA methylation patterns, which can affect gene expression and cellular function. Epigenetic alterations in the immune system, for example, can contribute to age-related decline in immune function and increased susceptibility to infection and chronic diseases.

Epigenetic alterations also play a role in developing and progressing various diseases, including cancer, heart disease, diabetes, and neurological disorders. In cancer, for example, epigenetic changes can silence genes that suppress tumour growth or activate genes that promote tumour growth, leading to uncontrolled cell growth and cancer development.

Studies on the nematode worm Caenorhabditis elegans have shown that altering the activity of genes involved in chromatin remodelling, a process that regulates the accessibility of DNA to transcriptional machinery, can impact lifespan.

Specifically, mutations that increase histone acetylation levels, a process that typically leads to transcriptional activation, can extend the lifespan of this organism.

Similarly, mutations that decrease the activity of histone demethylases, enzymes that remove methyl groups from histone proteins, can also extend the lifespan in C. elegans.

These studies suggest that alterations to chromatin structure and, by extension, gene expression, are integral to the ageing process.

Epigenetic alterations have also been observed in mammalian models of ageing. For instance, studies on mice have shown that epigenetic modifications to genes involved in mitochondrial function are associated with an ageing-related decline in energy metabolism.

These studies suggest that epigenetic alterations play a role in the decline of cellular function associated with ageing.

In addition to animal studies, studies on humans have also shown that epigenetic alterations are a hallmark of ageing. One of the most widely studied epigenetic changes in ageing is DNA methylation, which involves adding a methyl group to a cytosine base in DNA.

DNA methylation patterns change with age, with some regions of the genome becoming increasingly methylated while others become less methylated. These changes in DNA methylation have been shown to be associated with changes in gene expression characteristic of ageing.

Furthermore, studies have shown that epigenetic alterations can also be used as biomarkers of ageing. For example, DNA methylation-based clocks have been developed that accurately predict an individual’s age based on their epigenetic profile.

In addition, these clocks have been shown to predict mortality and morbidity risk better than chronological age alone, indicating that epigenetic alterations are intimately linked to the ageing process.

Overall, studies in animal models and humans have provided compelling evidence that epigenetic alterations are key in modulating the ageing process.