Do biochemical clocks accurately age children?
In medicine, we often use a person's chronological age - how many candles are on their birthday cake - as a guide to disease risk. But what really counts is a person's biological age: how well "lived in" is their body? A person who eats a poor diet, smokes, and breathes bad air is likely to age faster than someone without those exposures. And we can read various biochemical clocks, such as chemical changes to DNA, that correlate well with these sorts of insults, at least in adults. But what about in children? Are these markers helpful in this context, or does the process of development and growth make them harder to interpret? Imperial College's Oliver Robinson has been trying to find out…
Oliver - We had a very nice study. And actually I was quite involved in the early part of my career in getting it off the ground, but it was a Pan-European cohort. So now these children have been followed - currently the data I looked at, they were between five and 12 years old, but we had information since, since the pregnancy of the mothers. Over a thousand children with all these different biological and developmental measures.
Chris - What were the measures?
Oliver - There are many aspects to development. We looked at their height; we looked at fat mass; we did a range of cognitive tests; general fluid intelligence; and another test, which I really enjoyed watching the children do, 'cause it's extremely boring, they basically have to look at a whole screen of fishes and click if they see a fish pointing the other way. And you can see the children starting to squirm and wriggle 'cause they're getting really bored. But that's the whole point is to measure their attention. We looked at behaviour, tantrums, bullying, are they kind to each other? And then finally we looked at lung function as well.
Chris - What about biochemical markers, DNA methylation marks and so on. Were you appraising that too?
Oliver - Yeah, so we had four different markers, actually, DNA methylation; telomere length. And then we measured RNA - basically which genes are being read. And finally we looked at a range of chemicals in the blood, big molecules. So we are talking about proteins and metabolites. We combined all of these circulating markers, the proteins and metabolites and used this to develop a sort of average profile of children at different ages.
Chris - And when you do this, what trends emerge? Can you see a clear ageing-specific pattern? Do the markers hold true to what we think is the genuine age and developmental pathway or track these children on, and does it line up with what we see and have learned about adult ageing?
Oliver - I would say in many ways it does actually. As we know from many, many studies that telomere length and DNA methylation age reflect unhealthy aging. And in some respects we do see that it is harmful for the development of children. When I say harmful, I mean that actually, if you look at their behaviour, so how often they have tantrums and so on, this was greater for the children with the advanced biological age from these measures, that is showing that it's not really very good for, for their development, 'cause they're actually quite immature, perversely, if they have a mature DNA methylation age. So I think actually what is really happening with these measures is unhealthy environment is causing changes to these chemicals. I say this because we see for DNA methylation clock, I mean if the children's parents are smokers, they have an older DNA methylation age. And similarly for telomere length, if the parents are less wealthy, which might reflect a less beneficial environment, they actually have an older telomere length. So for these markers it seems that, as in adults, it's probably not a very good for children to be older biologically. But for some of the other markers we looked at, the chemicals circulating their blood, here actually it seemed to reflect developmental maturity. So we saw a strong association between older biological age using these markers with their working memory and their fluid intelligence.
Chris - So you've got certain suite of markers that appear to be quite good at telling us about developmental progress. You've also got a set of, or a suite of markers that seem to be quite good at pointing to exposure to potentially deleterious environments. So actually you could integrate both of these and you can ask in the same way as we plot, say head size and body weight on a growth chart, you can ask, is this child developing according to where we would expect them to develop, but also what insults are they having to weather as they go through and are, are there any things we can therefore try to put right?
Oliver - Exactly. And I think this is what's intriguing is showing that if they're less affluent and maybe there's a lower education environment in the family, which is all not optimal for children's development, we find that actually it has a real biological impact. So it is showing that it's really important to make sure that all these children have the best start in life.