Longevity Briefs: Can ‘Ageing Clocks’ Really Predict How Long You’ll Live?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

The underlying biological drivers of ageing appear to progress at different rates in different people, which may explain why some people seem to age more slowly than others. To describe this rate of ageing, scientists have come up with the concept of biological age – the number reflecting the extent to which ageing has progressed in your cells and tissues. The most common way of estimating someone’s biological age is to use an ‘epigenetic clock’. This is a technique that looks at patterns of DNA methylation – molecular ‘tags’ that are added and removed from the DNA over time and that correlate with chronological age – and uses them to produce an age estimate. Thus if someone has a chronological age of 50, but their DNA methylation patterns are equivalent to that of a typical 45 year-old, this could suggest that they are ageing at a slower pace than expected.

These epigenetic clocks can only provide an estimate of biological age, but they can still be useful in scientific studies investigating the effects of short-term interventions on the biology of ageing. Their relevance to human health is less clear. Many companies provide services that will measure your epigenetic age, allowing you to discover your ‘true biological age’ and take steps to reduce it. However, the extent to which this number actually predicts future health is less well established than other measurements you can easily obtain, such as blood pressure. Furthermore, there are practices that we know will lower blood pressure reliably, which will translate into reduced risk of cardiovascular disease. We need more research before we can say the same thing for a reduction in epigenetic age. In this study, which is available in preprint and has not yet been peer-reviewed, researchers looked at how well an epigenetic clock compared to various markers of health and ageing when it came to predicting subsequent mortality.

The discovery:

Researchers used data from the Berlin Aging Study II (BASE-II) in order to investigate 14 markers of ageing that were previously identified as suitable metrics for the success of interventions targeting ageing. The study involved 1,671 participants, all aged 60 years or older at the start of the study. Participants were followed up for an average of 7.4 years.

After controlling for confounding factors like age, sex and lifestyle factors, the markers that showed a statistically significant association with mortality were as follows:

• DunedinPACE, an epigenetic clock that is specifically designed to produce measurements that are predictive of future health
• IL-6, a marker of inflammation (which tends to increase with advancing age)
• Cognitive test scores
• Handgrip strength
• Standing balance

Out of all these markers, DunedinPACE was the strongest and most consistent predictor of mortality. This was true even when examining specific causes of death – for example, DunedinPACE correlated more closely with mortality from diseases of the circulatory system than did any of the other markers – though all of the markers mentioned did correlate with mortality. Combining just 3 measurements together (DunedinPACE, standing balance and muscle mass) was almost as predictive as all 14 measurements combined.

The implications:

The strong association of DunedinPACE with mortality in this study – a finding that is also supported by previous research – suggests that this epigenetic clock could have at least as much value for predicting future health as other well established predictors. There may therefore be some value to epigenetic clocks as a tool for predicting ‘ageing trajectories’. It is still somewhat unclear to what extend these measurements are actionable – that is to say, do interventions that slow down epigenetic ageing improve health, or are we just targeting something that happens to correlate with mortality?

DNA methylation changes can disrupt the expression of important genes, impairing cellular function. Experiments have also shown that erasing these changes in a process called ‘partial reprogramming‘ essentially makes old cells young again. These findings suggest that epigenetic changes probably contribute to ageing to some degree, but the extent to which we can affect this remains to be determined. Commercially available epigenetic ageing tests should still be interpreted with caution, as not all such tests use the same techniques, and there is no guarantee as to their reliability.