Longevity Briefs: Another Beneficial Compound Identified In Chocolate

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:

Chocolate is known to be rich in polyphenols – plant compounds that help protect against pathogens and damage caused by UV radiation. Polyphenols are of some interest when it comes to healthy ageing, since in animals they are able to lower inflammation and oxidative stress (damage caused primarily by harmful byproducts of normal metabolic processes). Both inflammation and oxidative stress are thought to play a role in the ageing process, being common features of most age-related diseases.

Polyphenols are not the only plant compounds with potential benefits – both coffee and cocoa contain a group of chemicals called methylxanthines. One such methylxanthine is caffeine, the consumption of which has also been found to be associated with healthy ageing. Cocoa doesn’t have much caffeine, but it does have large amounts of theobromine, another methylxanthine. In this study, researchers identify theobromine as potentially having an impact on estimated rates of biological ageing.

The discovery:

The study involved 509 female participants in the TwinsUK study, the largest adult registry of twins in the UK. They analysed the levels of 6 different methylxanthines in participants’ blood, and tested multiple methods for estimating participants’ rate of ageing. They found that theobromine levels showed statistically significant correlations with two biological ageing metrics. 

The first of these metrics was an epigenetic clock called GrimAge. Epigenetic clocks are algorithms that estimate how rapidly someone is ageing based on patterns of DNA methylation: molecular ‘tags’ that are added and removed from the DNA molecule throughout life. GrimAge differs from other epigenetic clocks in that it is optimised to produce measurements that are predictive of mortality. The researchers found that for participants with the highest theobromine levels, GrimAge’s estimate was on average around 1.5 years lower than participants’ actual (chronological) age, which could suggest that they were ageing more slowly on average.

The second method researchers used was DNAmTL, which also measures epigenetic modifications, this time to estimate telomere length. Telomeres are the protective caps on the ends of each chromosome, becoming shorter each time a cell divides, eventually preventing it from dividing any further. Faster rates of telomere shortening appear to correlate with faster rates of ageing. The researchers found that people with higher theobromine levels also had longer telomeres on average, suggesting that they may have undergone less shortening.

Since cocoa does contain small amounts of caffeine while coffee contains small amounts of theobromine, the researchers controlled for caffeine and its breakdown products and found that the above associations were still significant. They also controlled for other potential confounding factors such as BMI and age. Finally, researchers repeated their analysis in another larger cohort study, this time in 1160 German adults of both sexes, and found that the association was slightly stronger than in the first part of the study. 

The implications:

This study suggests higher blood levels of theobromine, most abundant in cocoa, are associated with a slower rate epigenetic ageing and longer telomeres. However, since this was an observational study, it’s impossible to say whether this was a causal effect of theobromine or something else. People with higher blood levels of theobromine are likely to be consuming more theobromine-rich foods, which may contain other beneficial compounds that weren’t controlled for. They might consume healthier diets in general, or they might have healthy metabolic traits that happen to influence theobromine levels.

Another thing to keep in mind is that lower epigenetic age and increased telomere length do not guarantee that someone is ageing at a slower pace – they are simply estimates that are known to correlate with age across the human population. With these caveats aside, theobromine has been shown to extend lifespan in worms and also appears to have some health benefits in mice. It’s therefore plausible that theobromine might be having some beneficial effects on the ageing process.