With the advent of epigenetic clocks that appear able to measure biological age, researchers are interested in putting these clocks to work on the assessment of interventions that might affect the pace and state of aging. It is the case, of course, that today there are all too few interventions that can reliably affect the pace and state of aging. But, arguably, the research community shouldn’t let that get in the way of generating data with the interventions that do exist, such as exercise, calorie restriction, or senolytics, even though the effects on longevity in humans are either small or unknown.
The most important challenge in the use of epigenetic clocks is that it remains somewhat unclear as to what exactly it is that these clocks are measuring. In other words which of the underlying mechanisms of aging contribute to the observed epigenetic changes that are characteristic of aging, and the relative size of their contributions. Some researchers, on the other hand, and as is the case here, think that epigenetic changes are an underlying cause of aging, and that puts a different spin on assessing these changes. To some extent the motivation doesn’t matter in this case: gathering more data, and particularly data on combinations of interventions, may be a decent first step towards making better use of epigenetic age assessments.
Josh Mitteldorf’s latest initiative, The Data-BETA Project, is a bold attempt to learn how a wide range of supplements, dietary changes, and exercise regimes are actually impacting our biological age. “Up until a few years ago, we really only had animal studies to go on for life extension. And then it was a major revolution when Horvath came out with his first methylation clock. The second generation of that clock called the PhenoAge clock came out two years ago and that is what inspired me to think about this study. The crucial point is that the methylation profile derived from PhenoAge is an even better predictor of when you’re going to die than PhenoAge itself. So, and this is a theme that I’ve been putting out there, that’s a deep indication that methylation is a driver of aging, and potentially a deeper cause of aging than things like autoimmunity, inflammation, blood pressure, blood sugar, and so on.”
As a result, Mitteldorf believes that time is now right to start using methylation clocks to start evaluating anti-aging programs to see what works – and what doesn’t. This belief led him to the creation of the Data-BETA Project – a proposed 5,000 person study that will use methylation clocks to measure the anti-aging impact of a wide range of interventions. Importantly, the study will also explore the potential impact of combinations of interventions to produce a bigger anti-aging benefit than the sum of their separate effects. “People have been caught up in this model of studying one intervention at a time, but I think biology doesn’t work that way. Biology really is much more holistic than that. We should be looking at combinations of treatments and not expect that there’s going to be a single chemical and that’s going to solve aging for us. We’re much more likely to make progress if we look at combinations of treatments and the interactions from the get-go – not just what the treatment does separately.”