The Epigenetics Revolution

There are thus two separate aspects to any scientific discussion of ageing. These are lifespan itself, and the control of late-onset disorders associated with ageing. What isn’t clear is the degree to which it is possible or reasonable to separate the two, at least in humans.

Epigenetics definitely has a role to play in ageing. It’s not the only factor that’s important, but it is significant. This field of epigenetics and ageing has also led to one of the most acrimonious disputes in the pharmaceutical sector in recent years, as we’ll see towards the end of this chapter.

We have to ask why our cells malfunction as we get older, leaving us more at risk of illnesses that include cancer, type 2 diabetes, cardiovascular disease and dementia, amongst a host of other conditions. One reason is because the DNA script in the cells of our body begins to change for the worse. It accumulates random alterations in sequence. These are somatic mutations, which affect the tissue cells of the body, but not the germline. Many cancers have changes in the DNA sequence, often caused by quite large rearrangements between chromosomes, where genetic material is swapped from one chromosome to another.

Guilt by association

But as we’ve seen, our cells contain multiple mechanisms for keeping the DNA blueprint as intact as possible. Wherever possible, a cell’s default setting is to maintain the genome in its original state, as much as it can. But the epigenome is different. By its very nature, this is more flexible and plastic than the genome. Because of this, it is probably not surprising that epigenetic modifications change as animals age. The epigenome may eventually turn out to be far more prone to changes with age than the genome, because the epigenome is more naturally variable than the genome anyway.

We met some examples of this in Chapter 5, where we discussed how genetically identical twins become less identical epigenetically as they age. The issue of how the epigenome changes as we age has been examined even more directly. Researchers studied two large groups of people from Iceland and from Utah, who have been part of on-going long-term population studies. DNA was prepared from blood samples that had been taken from these people between eleven and sixteen years apart. Blood contains red and white blood cells. The red blood cells carry oxygen around the body, and are essentially just little bags of haemoglobin. The white blood cells are the cells that generate immune responses to infections. These cells retain their nuclei and contain DNA.

The researchers found that the overall DNA methylation levels in the white blood cells of some of these individuals changed over time. The change wasn’t always the same. In some individuals, the DNA methylation levels went up with age, in others they dropped. The direction of change seemed to run in families. This may mean that the age-related change in DNA methylation was genetically influenced, or affected by shared environmental factors in a family. The scientists also looked in detail at methylation at over 1,500 specific CpG sites in the genome. These sites were mainly associated with protein-coding genes. They found the same trends at these specific sites as they had seen when looking at overall DNA methylation levels. In some individuals, site-specific DNA methylation was increased whereas in others it fell. DNA methylation levels were increased or decreased by at least 20 per cent in around one tenth of the people in the study.

The authors stated in their conclusion that ‘these data support the idea of age-related loss of normal epigenetic patterns as a mechanism for late onset of common human diseases’[237]. It’s true that the data are consistent with this model of epigenetic mechanisms leading to late onset disease, but there are limitations, which we should bear in mind.

In particular, these types of studies highlight important correlations between epigenetic change and diseases of old age, but they don’t prove that one event causes the other. Deaths through drowning are most common when sales of suntan lotion are highest. From this one could infer that sun tan lotions have some effect on people that makes them more likely to drown. The reality of course is that sales of suntan lotion rise during hot weather, which is also when people are most likely to go swimming. The more people who swim, the greater the number who will drown, on average. There is a correlation between the two factors we have monitored (sales of sun block and deaths by drowning) but this isn’t because one factor causes the other.