Biological clocks to measure ageing

Ageing is an inevitability; but what’s the best way to measure it? We know that the number of years someone’s been alive is one way, but that’s only a measure of chronological age. We also have a “biological age” - how our lifestyles, sex and genes - influence the equation, and there are a number of different biological clocks ticking in the body to refer to: things like how our DNA changes across the life course, or how proteins alter their configurations. Do all these clocks tick in sync though, and do some do a better time-keeping job than others? To try to find out, Laura Han, at the Amsterdam University Medical Centre, has been using machine learning systems to marry up what the different biological clocks say about information collected from a large dataset called the Netherlands study of depression and anxiety, as she told Chris Smith...

Laura - What is unique about this cohort is that we've collected a lot of biological information, and this is also the information that we have used to develop and examine the so-called biological clocks. The biological clock is actually a predictive machine learning algorithm that has learned biological patterns in our bodies that are correlated to age, DNA methylation levels, or proteins or metabolites.

Chris - And what were you comparing with what? So if you've got those sorts of markers or those sorts of measurements, what are you comparing them to?

Laura - This algorithm - you train it and it is able to predict your age based on these biological patterns. And when it actually predicts you to be older than your actual age, then it kind of suggests that you have an older appearing biological state, or at least the state that is normally seen in older people.

Chris - And can you then marry that up to potential causative factors?

Laura - Yeah, exactly. So if you think about biological ageing in that way, you might be able to say that the ticking rate of your biological clock might be faster than time itself.

Chris - Are there some people who, for want of a better phrase, have a very well lived in body so they look a lot older than they really are, but it doesn't actually translate into dying next week? They look terrible, but actually they're still going to go on forever. So does does just sort of one marker of ageing translate to everything or could that be misleading?

Laura - It could be misleading and this was also one of the main questions that we wanted to ask with our data set. We had multiple markers of biological ageing, and we wanted to see if those were kind of in sync with each other. So are the same factors associated with the ticking rate of all biological clocks.

Chris - You've alluded to what some of these clocks are. So what were the main things that you were assessing and appraising in the study then, what were the clocks that you looked at?

Laura - So we looked at five different cellular biological clocks, one of them being telomere length. And this is basically a cap on the end of your chromosome that shortens as we age. And this is a very well studied marker of biological ageing. And then we have four different, what we call, omics levels of ageing - DNA methylation in our blood, or the protein levels,, or gene expression levels or metabolites. And these can be used more in a modern type of way to quantify biological ageing, because we can use these predictive algorithms to learn what kind of patterns are really correlated to age.

Chris - And when you marry them up with the sorts of factors, the lifestyle factors and others, that associate with the people from which these measurements are coming, how good are these clocks and what sorts of things do tend to speed them up or slow them down?

Laura - Being male, and having a high body mass index, so obesity. Smoking and having a metabolic syndrome were most consistently linked with older appearing biology across multiple clocks.

Chris - How about one of the things you have alluded to which is how you feel, because, you know, there is this saying you're only as old as you feel. Is there any truth in that when you actually look at people who are depressed and miserable compared to people who take a much more rose-tinted outlook on life, do you see that reflected in these biological clocks?

Laura - Yeah. So this is actually a very good question, and what we see in depressed patients is that they carry a higher risk to develop age-related diseases. And in our study we actually confirmed that depression was linked to older appearing biology as well, measured by at least three of the five biological clocks. And I think that this really confirms that biological ageing is linked to both mental and physical health, and also might offer an explanation as to why we see higher risks of age-related diseases in depression.

Chris - What would you therefore say that the take home message here is then? You've appraised these different independent biological clocks, you've married them up to some of the risk factors that make them tick faster or slower, but what's the take home message? What do you conclude?

Laura - I think the take home message is that many other studies have looked at individual quantifications of ageing, so individual biological clocks, and only a few have integrated multiple biological clocks in the same study population. And we found that of the five biological ageing indicators, only three were found to significantly interact with each other meaning that an increase in one indicator also paralleled an increase in the other. But also these correlations were quite small. So I think it really highlights that ageing and the ageing process is really complex and it's still relatively unknown whether different clocks measure the same thing and how they interact and influence each other. And what we found is that if you are measured to be biologically older by multiple clocks, this actually also has a cumulative effect. So on your overall well-being in terms of physical and mental health.