101 Facts About Ageing #39: The Way Our DNA Is Read Changes With Age

As Daniel Patrick Moynihan, an American sociologist, politician, and diplomat once said: “Everyone is entitled to his own opinion, but not his own facts”. And we wholeheartedly agree. A shared set of facts is the first step to building a better world with longevity for all. In that spirit, we are creating a series that covers 101 indisputable facts about ageing, health and longevity.

Every cell in the human body contains the same genetic code, yet even within a single tissue, there exist many cell types that can be vastly different from one another. This is possible because, while each cell contains the full DNA instruction manual, not all cells are reading the same pages. The extent to which different parts of the genetic code are accessible to be ‘read’ is controlled by epigenetic alterations: chemical and structural changes to the DNA strand that don’t alter the genetic code itself.

There are three main types of epigenetic alteration:

• DNA methylation, a process that works directly on the DNA sequence. Chemical compounds called methyl groups can be added to genes in a way that turns them on or off. In either case, the addition of a new chemical group affects how a region of DNA is recognised and read by the cell’s protein-synthesising machinery.
• Histone modification. The two metres of DNA within each of our cells is tightly wound around proteins called histones to form a compact structure called chromatin. Histones can have a variety of chemical tags attached to them, which changes how tightly or loosely they pack the DNA. A loosely packed region of DNA is more accessible to be read by the protein-synthesising machinery, while the reverse is true for tightly packed DNA.
• RNA and proteins, themselves products of gene expression, can in turn regulate the activity of genes.

The type and distribution of these epigenetic alterations is not stable: it changes throughout an organism’s life, thereby changing the expression of genes in ways that are mostly deleterious to the organism. Important genes could be turned off, thereby causing cells to function poorly or die. Conversely, epigenetic changes can render a gene overactive and result in transcriptional noise – essentially, the gene is expressed so strongly that it drowns out other more important genes. Studies have found age-associated changes in the expression of genes involved in inflammation, mitochondrial function and lysosomal degradation (the cell’s ‘garbage disposal’ system, used to remove damaged components). Through these changes, epigenetic alterations may impair cellular function and promote age-related disease.

What causes these epigenetic changes to occur? In fact #26, we covered how the genetic code is constantly being damaged and repaired. Unfortunately, even when damage to the DNA is patched up, epigenetic changes can be left behind. This is especially true when both of the DNA strands are broken, which can lead to the epigenetic shutting down of entire genes. We also know that lifestyle factors such as diet, exercise and stress can affect epigenetic alterations. Some individuals can undergo the epigenetic changes associated with ageing at a more rapid pace than others, but we are still in the process of figuring out to what extent these alterations contribute to the functional decline during ageing.